Stereotactic hypothalamic obesity probe

ABSTRACT

Apparatus and methods for regulating the appetite of an individual suffering from morbid obesity, the apparatus including a plurality of stimulation electrodes arranged longitudinally on at least one electrode support shaft for insertion within the hypothalamus for outputting electrical discharges to specific sites within the hypothalamus. Each of the plurality of stimulation electrodes may be independently controlled. Electrical discharge of various frequencies transmitted from one or more of the plurality of stimulation electrodes, and delivered to a region of the hypothalamus that is involved with either stimulating or inhibiting appetite, may be used to regulate appetite in the individual. Alternatively, an individual&#39;s appetite may be regulated by the microinfusion from at least one microinfusion catheter of an appropriate quantity of a suitable drug to a distinct site or region within the hypothalamus.

RELATED U.S. APPLICATION DATA

This Application is a Divisional of U.S. patent application Ser. No.08/884,654 filed Jun. 27, 1997, now U.S. Pat. No. 6,129,685, which is acontinuation-in-part of U.S. patent application Ser. No. 08/549,165filed Oct. 27, 1995, U.S. Pat. No. 5,843,093, which is acontinuation-in-part of U.S. patent application Ser. No. 08/332,755filed Nov. 1, 1994 U.S. Pat. No. 5,697,975, which is acontinuation-in-part of U.S. patent application Ser. No. 08/194,017filed Feb. 9, 1994, now U.S. Pat. No. 5,496,369, the contents of each ofwhich are incorporated herein by reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates generally to an apparatus and method fordelivering and detecting electrical signals to/from the patient's brain.In one embodiment, this invention also relates to an apparatus andmethod for performing ablative surgery on a patient. In particular theinvention is concerned with an apparatus and method for performing brainsurgery; and more particularly the invention is concerned with anapparatus and method for performing brain surgery by monitoring andselectively inactivating specific regions within the brain. Theinvention is also concerned with an apparatus and method for deliveringtherapeutic drugs, and more particularly is concerned with an apparatusand method for delivering therapeutic drug to a specific region within apatient's brain tissues, by monitoring and selectively delivering a drugto the target tissue. In one embodiment, this invention also relates toan apparatus and method for selective electrical stimulation of apatient's hypothalamus for the purpose of appetite regulation. In yetanother embodiment, this invention relates to an apparatus and methodfor localized drug treatment for the purpose of appetite regulation bydrug microinfusion into certain regions of the hypothalamus.

2. Background of the Related Art

Prior to the nineteenth century, physicians and scientists believed thebrain was an organ with functional properties distributed equallythrough its mass. Localization of specific functions within subregionsof the brain was first demonstrated in the 1800's, and provided thefundamental conceptual framework for all of modern neuroscience andneurosurgery.

As it became clear that brain subregions served specific functions suchas movement of the extremities, and touch sensation, it was also notedthat direct electrical stimulation of the surface of these brain regionscould cause partial reproduction of these functions. Morgan, J. P., “Thefirst reported case of electrical stimulation of the human brain,” J.History of Medicine, January 1982:51–63, 1982; Walker, A. E., “Thedevelopment of the concept of cerebral localization in the nineteenthcentury,” Bull. Hist. Med., 31:99–121, 1957.

Brain Mapping Studies

The most extensive work on electrical stimulation “mapping” of the humanbrain surface was carried out over several decades by Dr. WilderPenfield, a neurosurgeon and physiologist at the Montreal NeurologicalInstitute, mostly during the early to mid-1900's. He made preciseobservations during cortical stimulation of hundreds of awake patientsundergoing brain surgery for intractable epilepsy. Among his manyfindings, he noted that stimulation of the visual and hearing areas ofthe brain reproducibly caused the patients to experience visual andauditory phenomena. Penfield, W. et al., “Somatic motor and sensoryrepresentation in the cerebral cortex of man as studied by electricalstimulation,” Brain 60:389443, 1937; Penfield, W. et al., Epilepsy andthe Functional Anatomy of the Human Brain, London: Churchill, 1954;Penfield, W. et al., “The brain's record of auditory and visualexperience,” Brain, 86:595–696, 1963. Following the results of earlyhuman brain mapping studies, electrical stimulation of sensory brainregions to restore lost function was a logical therapeuticextrapolation. Drs. Brindley and Lewin of the University of Cambridgewere the first to reduce the concept to practice by implanting a patientwith a visual cortex neural prosthetic device. Brindley, G. S. et al.,“The sensations produced by electrical stimulation of the visualcortex,” J. Physiol. 196:479493, 1968. Their device consisted of anarray of thin, flat electrodes placed on the surface of the visualcortex. The electrodes were remotely controlled with radio signals. Asimilar system was later tested at the University of Utah by Dr. Dobelleand colleagues. Dobelle, W. H. et al., “Artificial vision for the blind:stimulation of the visual cortex offers hope for a functionalprosthesis,” Science 183:440444, 1974.

Findings from these early British and American studies were consistent.Patients reliably perceived flashes of light (phosphenes) during periodsof electrical stimulation, and simple patterns of phosphenes could begenerated by simultaneously activating multiple contacts. While thesefindings strongly suggested the eventual feasibility of a corticalvisual prosthetic device, many important design problems wereinsurmountable at that time.

Among these were an inability to precisely stimulate very small volumesof brain, the requirement for high stimulation currents to inducephosphenes, and an inability to access the patient's full “visual space”with the large array of surface electrodes used. Additionally, therewere no miniature video cameras and small, powerful computers at thetime capable of converting visual images into complex electricalstimulation sequences at ultra high speed.

Penetrating Electrodes as Neural Prostheses

The University of Utah has discontinued visual cortex prosthesesresearch. However, the concept has been pursued at NIH where significantadditional advances have been made. Their most important discovery todate relates to the use of needle shaped penetrating depth electrodesinstead of flat surface stimulating electrodes. Bak, M., et al., “Visualsensations produced by intracortical microstimulation of the humanoccipital cortex,” Med. Biol. Eng. Comput., 28:257–259, 1990.Penetrating electrodes represent a major design improvement. They areplaced within the brain tissue itself so there is optimal surfacecontact with elements of the brain that are targeted for stimulation. Asa result, patients perceive visual phosphenes with approximately athousand-fold less stimulation current than that required when surfaceelectrodes are used. This allows for safe, chronic stimulation of verysmall discrete volumes of brain.

Additionally, penetrating electrodes transform what was in the past atwo dimensional implant-brain interface (flat disks on the surface ofthe brain) into a three dimensional interface (multiple needle-likeelectrodes in parallel extending from the surface into the brainsubstance), which vastly increases the device's access to stimulationtargets below the surface. To use a television screen analogy, a twodimensional surface-electrode array may have the potential of generatingan image on the “screen” composed of approximately one hundred discreetdots (“pixels”), whereas a three-dimensional array would potentiallygenerate an image with many thousands of dots. The huge potentialincrease in image resolution would be achieved using a small fraction ofthe stimulation currents used in the past.

Penetrating electrodes have the potential to markedly increase bothimage quality and the safety of the stimulation process. Humanexperimental studies continue at the NIH campus. Extramural NIH fundingis also directed at supporting engineering research on penetratingelectrodes optimally suited for neural prosthetics applications. TheUniversity of Michigan, for example, has made use of computer-chipmanufacturing techniques to synthesize exquisitely small electrodearrays. The etched electrical contacts on these devices are so smallthat the distance separating adjacent contacts can be in the range of 50micrometers, approximately the diameter of two nerve cell bodies. Drake,K. L. et al., “Performance of planar multisite microprobes in recordingextracellular single-unit intracortical activity,” IEEE Trans. BME,35:719–732, 1988.

During the 1970's the neural prosthetics group at the University of Utahnot only explored the feasibility of a visual cortex neural prostheticdevice, but carried out experiments in auditory cortex stimulation aswell. Led by Dr. Dobelle, they formed a mobile research group thattraveled to surgical centers throughout the United States when suitableexperimental subjects were identified. These were patients who requiredtemporal lobe surgery for tumor removal or treatment of intractableepilepsy, and who agreed to participate in the experimental protocol.Dobelle, W. H. et al., “A prosthesis for the deaf based on corticalstimulation,” Ann. Otol, 82:445463, 1973.

The primary auditory region of the human brain is buried deep within theSylvian fissure. It is not visible from the brain surface and its exactlocation varies slightly from one person to the next. MRI and CTscanners were not invented at the time of Dr. Dobelle's experiments sothe anatomy of the patients' auditory cortex could not be studied priorto surgery, and this region could only be visualized with difficulty inthe operating room after the Sylvian fissure was surgically dissected.Once the buried auditory cortex was exposed, surface stimulatingelectrodes were placed by hand over the area thought to be auditorycortex and the brain was stimulated in a fashion similar to that used togenerate visual phosphenes.

Reproducible sound sensations were generated in the experimentalsubjects. Though these preliminary findings were encouraging, a range oflimitations precluded further work by this group. Among the moredaunting problems the Utah group faced were recruiting suitable patientsfor the experimental study and obtaining good stimulationcharacteristics from the experimental surface electrodes. The minimalstimulation threshold for eliciting sound sensations was found to be 6milliamperes, which is too high to be tolerated chronically and isthousands of times greater than currents found subsequently to berequired to generate phosphenes in visual cortex using penetratingelectrodes.

Recent advances in MRI and computer technology now allow detailedpreoperative imaging of human auditory cortex.

Another major technical innovation developed since the time of Dr.Dobelle's early experiments is the cochlear implant. An important aspectof the cochlear implant technology, which is now highly refined,involves transducing sound into complex electrical stimulationsequences. This large body of technical knowledge developed over thelast twenty years will be directly applicable to the auditory cortexprosthetic device and aid immeasurably in its research and development.

Normal Hearing

Mechanisms of human hearing are reviewed briefly to provide a frameworkfor discussion of auditory neural prosthetic devices. The auditorysystem is composed of many structural components that are connectedextensively by bundles of nerve fibers. The system's overall function isto enable humans to extract usable information from sounds in theenvironment. By transducing acoustic signals into electrical signalsthat can then be processed in the brain, humans are able to discriminateamongst a wide range of sounds with great precision.

FIGS. 1A and 1B show a side and front view of areas involved in thehearing process. In particular, the normal transduction of sound wavesinto electrical signals occurs in cochlea 110, a part of the inner earlocated within temporal bone (not shown). Cochlea 110 is tonotopicallyorganized, meaning different parts of cochlea 110 respond optimally todifferent tones; one end of cochlea 110 responds best to high frequencytones, while the other end responds best to low frequency tones. Cochlea110 converts the tones to electrical signals which are then received bycochlea nucleus 116. This converted information is passed from cochlea110 into brain stem 114 by way of electrical signals carried along theacoustic nerve and in particular, cranial nerve VIII (not shown).

The next important auditory structure encountered is cochlea nucleus 116in the brain stem 114. As the acoustic nerve leaves the temporal boneand enters skull cavity 122, it penetrates brain stem 114 and relayscoded signals to cochlear nucleus 116, which is also tonotopicallyorganized. Through many fiber-tract interconnections and relays (notshown), sound signals are analyzed at sites throughout brain stem 114and thalamus 126. The final signal analysis site is primary auditorycortex 150 situated in temporal lobe 156.

The mechanisms of function of these various structures has also beenextensively studied. The function of cochlea 110 is the mostwell-understood and the function of primary auditory cortex 150 is theleast understood. For example, removal of the cochlea 110 results incomplete deafness in ear 160, whereas removal of primary auditory cortex150 from one side produces minimal deficits. Despite extensive neuralconnections with other components of the auditory system, primaryauditory cortex 150 does not appear to be necessary for many auditoryfunctions.

Cochlear Implant

Cochlear implants were designed for patients who are deaf as a result ofloss of the cochlea's sound transduction mechanism. Implant candidatesmust have an intact acoustic nerve capable of carrying electricalsignals away from the middle ear into the brain stem. The deviceconverts sound waves into electrical signals which are delivered througha multi-contact stimulating electrode. The stimulating electrode issurgically inserted by an otolaryngologist into the damaged cochlea.Activation of the contacts stimulates acoustic nerve terminals whichwould normally be activated by the cochlear sound transductionmechanism. The patient perceives sound as the coded electrical signal iscarried from the middle ear into the brain by the acoustic nerve. Cohen,N. L. et al., “A prospective, randomized study of cochlear implants,” N.Engl. J. Med., 328:233–7, 1993.

In patients with hearing loss caused by dysfunction at the level of thecochlea, cochlear implants can be remarkably effective in restoringhearing. For example, some previously deaf patients are able tounderstand conversations over the telephone following insertion of acochlear implant.

Cochlear implants are surgically placed in the middle ear which issituated in the temporal bone. In patients who are already deaf, thereis very little chance of any additional injury being caused by placementof a cochlear implant; they are very safe devices. Because of the lowhealth risk associated with placing cochlear implants, obtainingexperimental subjects during the early development stage was notdifficult. In this setting design improvements occurred rapidly.

Cochlear Nucleus Implant

Patients are not candidates for cochlear implants if their hearing lossresults from damage in auditory regions other than the cochlea. Becausethe first auditory relay station “downstream” from the cochlea andauditory nerve is the brainstem cochlear nucleus, this structure is alogical candidate for consideration as an implantation site. Thisapproach was first developed at the House Ear Institute. Eisenberg, L.S. et al., “Electrical stimulation of the auditory brainstem structurein deafened adults,” J. Rehab. Res. 24:9–22, 1987; Hitselberger, W. E.et al., “Cochlear nucleus implant,” Otolaryngol. Head Neck Surg.,92:52–54, 1984. As is the case with cochlear implants, sound waves aretranslated into a complex electrical code F. The implant's stimulationterminals are placed up against the cochlear nucleus, and the patientperceives sounds when the system is activated.

Data on efficacy is limited because relatively few patients have beentested with this device. Early findings demonstrate, however, that somedegree of useful hearing is restored using this device. Environmentalsounds such as a knock at the door and a telephone ringing have beendetected by patients with a cochlear nucleus implant, and this improvedauditory function has increased patients' ability to live independently.

Although work in the visual cortex demonstrates that central nervoussystem penetrating electrodes are significantly more effective thansurface electrodes, use of penetrating electrodes in the cochlearnucleus has been discontinued for safety reasons described below.

For several reasons, there is significantly more risk associated withcochlear nucleus implants than cochlear implants. The cochlear nucleusis situated in the brain stem; a very sensitive and vital structure.Neurosurgical procedures in the brain stem are among the most difficultand dangerous operations performed. Infiltrating tumors within thesubstance of the brainstem, for example, are usually consideredsurgically inoperable. Surgical manipulation or injury of brainstemelements can cause devastating complications, including loss of normalswallowing functions, loss of control of eye movements, paralysis, coma,and death.

Because of their internationally renowned acoustic neuroma practice,doctors at the House Ear Institute are among the most experiencedsurgeons in the world at gaining surgical access to the brainstemsurface. Acoustic neuromas are tumors arising from the supporting cellsof the acoustic nerve. As they enlarge, these tumors expand into thecranial cavity and press up against the brainstem. Patients typicallypresent with hearing loss, and a number of surgical approaches have beendeveloped by otolaryngologists and neurosurgeons to remove theselesions.

Surgeons at the House Ear Institute have played a pioneering role inacoustic neuroma surgery and now routinely perform operations where thetumor is safely removed and the brainstem surface is visualized. Theyhave placed cochlear nucleus implants in deaf patients who have lostfunction of both acoustic nerves and are undergoing removal of anacoustic neuroma. This affords access to the brainstem surface during amedically necessary procedure.

The first cochlear nucleus implant used penetrating electrodes. Thesefunctioned well initially, however within two months they had migratedfurther into the brainstem, causing tingling sensation in the patient'ship as adjacent fiber tracts were inadvertently stimulated. This systemwas removed and surface electrodes have been used for cochlear nucleusimplants since that time. Risks of implanting a cochlear nucleus deviceare such that patients are only candidates for implantation if theyrequire surgery in that area of the brainstem for some other, usuallylife threatening reason.

It is difficult to find suitable patients for implantation and testingof cochlear nucleus implants. The most likely candidates are patientswho have a rare form of neurofibromatosis and acoustic neuromas on bothacoustic nerves. Martuza, R. L. et al., “Neurofibromatosis 2 (bilateralAcoustic Neurofibromatosis),” N. Engl. J. Med., 318:684–688, 1988. Asmall number of these patients are referred regularly to suchinstitutions as the House Ear Institute. Many university medicalcenters, however, would be unable to identify a single suitablecandidate during a full year. In the fourteen years since its initialclinical application at the House Institute, cochlear nucleus implantuse and testing has remained quite restricted (less than two implantsper year average during the epoch reported in Eisenberg, L. S. et al.,“Electrical stimulation of the auditory brainstem structure in deafenedadults,” J. Rehab. Res. 24:9–22, 1987.

Treating Deafness

Devices designed to treat deafness must take into consideration theunderlying cause of deafness. For example, a patient with defectivecochlea 110 who still has a functional acoustic nerve, may benefit froman artificial cochlea (cochlear implant). However, if the acoustic nerveis damaged and cannot carry electrical signals, then the problem is “toofar downstream” in the signal processing sequence for a cochlear implantto be effective. In that situation, artificial signals must enter theauditory system “beyond the block” either in brain stem 114 or inauditory cortex 150.

Parkinson's Disease

Parkinson's disease is a neuropathological condition of unknownaetiology which afflicts approximately 1 million individuals in the U.S.alone. Symptoms include a paucity of spontaneous movement(bradykinesia), rigidity, and tremor, which in many cases can be verydisabling. The average age of onset is 57, with about 30% of cases beingdiagnosed before age 50. Since the 1960's a number of different drugshave been used for the treatment of Parkinson's disease. Drug treatmentof Parkinson's disease may ameliorate some of the symptoms, but does notprovide a cure for the disease. Furthermore, drugs used for thetreatment of Parkinson's disease tend to become less effective inalleviating symptoms over time and often result in severe side effects.For example, L-dopa which has been widely used for the treatment ofParkinson's disease over the past 30 years, is associated with sideeffects which include uncontrollable muscular contraction of the limbsand face. And, with the passage of time many, perhaps all, patients failto respond well to L-dopa treatment.

Prior Art Surgical Treatment of Parkinson's Disease

Surgical treatment by neurosurgeons to treat Parkinson's disease has itsroots in the observation that some patients exhibited decreased symptomsafter experiencing a mild stroke. A widely accepted explanation for thisobservation is that the stroke caused destruction of fiber tracts orgroups of neurons which had been conducting or generating abnormalsignals. Early attempts to treat Parkinson's disease by selectivelyinactivating certain parts of the brain gave mixed results. The poorresults obtained can be ascribed to a number of causes, particularlyincluding poor targeting of brain tissue to be inactivated andimprecision in the design and use of the surgical probes.

Neurosurgeons at a number of medical centers worldwide are currentlyperforming stereotactic thalamotomy or pallidotomy for the treatment ofParkinson's disease, in which regions within the target tissue (thalamusor globus pallidus) of the patient's brain are surgically accessed,physiologically monitored, and targeted for localized tissue destruction(L. Y. Laitinen, et al., “Leksell's Posteroventral Pallidotomy in theTreatment of Parkinson's Disease,” J. Neurosurg., 76, 53–61 (1992), R.P. Iacono, et al., “The Results, Indications, and Physiology ofPosteroventral Pallidotomy for Patients with Parkinson's Disease,”Neurosurgery, 36, 1118–1127 (1995), and references cited therein).

FIG. 12A shows the gross morphology, relative size and approximatelocation of the globus pallidus. The globus pallidus is a conicalsubcortical structure which is involved in the control of movement. FIG.12B shows the gross morphology, relative size and approximate locationof the thalamus. The thalamus is a relatively large ovoid body which,inter alia, relays sensory stimuli to the cerebral cortex.

Prior Art Stereotactic Pallidotomy

The currently used prior art procedure is quite complex and cumbersome.Briefly, it involves a preliminary step of obtaining microelectroderecordings from specific regions within the globus pallidus. Then,depending on the electrical potential(s) recorded from the particularregion under study, the microelectrode is removed, and a macroelectrodeis introduced into the same region of the globus pallidus to create alesion thereat, thereby causing localized tissue destruction andirreversible inactivation of neurons in that region. This process mustbe repeated a number of times in order to obtain an appropriate “sample”of the globus pallidus.

According to the prior art stereotactic techniques, the trajectories ofthe introduced electrodes are perpendicular to the long axis of theglobus pallidus, as shown in FIG. 12C. The prior art techniquestherefore entail the surgeon making several passes through normal braintissue. In addition, the electrode trajectories of the prior arttechniques are the least useful with respect to sampling the targetvolume. Furthermore, the use of separate electrodes for monitoringneuron physiology (microelectrode) and for producing lesions(macroelectrode) is inefficient, time consuming, and is prone to errorin positioning the macroelectrode.

Hypothalamic Obesity Probe

While malnutrition is known as a serious problem in many underdevelopednations, obesity has been referred to as the major nutritional disorderof the developed world. This disorder is extremely prevalent:approximately one in three, or about 33%, of the population in the U.S.are overweight. Obesity is known to have serious adverse effects onhealth, and is associated with increased morbidity and mortality from anumber of diseases and physiological conditions, includingcardiovascular disease, stroke, coronary infarction, hypertension,diabetes, and hypercholesterolemia. {See, for example, Manson et al., N.Engl. J. Med. 333:677–685; 1995 OPTIONALLY OMIT CITATION.} In most casesa quantitative relationship exists showing a positive correlationbetween body weight of an individual of a given height and a particularhealth risk to that individual, i.e., the heavier the individual, thegreater the risk. Apart from health-related factors discussed above,obesity is also undesirable in that it restricts mobility of theafflicted individual, and in addition can be a source of unacceptance,ridicule, and discrimination in certain societies.

Simply stated, weight gain in the otherwise healthy person is typicallydue to a net positive caloric balance, ie., the total caloric content offood ingested exceeds the number of calories “burned” during metabolismover a defined period of time. It is not uncommon for an obese person tobe as much as 30 Kg overweight. In order to lose 30 Kg of adipose tissue(fat), a negative net energy balance of about 210,000 Kcal (210,000calories) is required. Naturally, it will require a period of severalmonths to achieve weight loss on these proportions.

Current approaches to treating obesity include one or more of thefollowing: adherence to a reduced calorie diet (with or withouttreatment with appetite suppressant drugs); lifestyle change, such asincreased exercise regime; and surgery. The approach adopted for any oneindividual will depend on the degree of obesity, age of the individual,and other factors.

Morbid obesity is a prevalent, debilitating, and life threateningdisorder for which surgical procedures may be indicated. Currentsurgical treatments involving the gastrointestinal tract seek todecrease the patient's ability to absorb calories from ingested caloricmaterial (food and beverages). Such treatments comprise major surgicalprocedures which themselves carry considerable risk of mortality andmortality, and in addition such procedures often prove to beineffective.

Apart from surgical procedures for the treatment of obesity, a number ofattempts have been made to treat certain disturbances or disorders,including appetite disorders, by various forms of electrical stimulationof the head, CNS, or brain of a patient. For example, U.S. Pat. No.5,540,734 discloses electrical stimulation of one or both of thetrigeminal and glossopharyngeal nerves via one or more electrodesattached thereto. Such electrical stimulation is disclosed to serve as ameans to treat, control or prevent various disorders (psychiatric,neurological, etc.), including eating disorders such as compulsiveovereating. U.S. Pat. No. 5,443,710 discloses a method for treatingvarious disorders, including appetite intrusiveness, by use ofelectroencephalographic disentrainment feedback to “exercise” thepatient's brain, wherein the term “disentrainment” refers to thedisruption of entrained brain wave patterns. U.S. Pat. No. 5,332,401discloses an apparatus and method for transcranial electrotherapy(TCET), wherein the apparatus includes a skin electrode mounting system,e.g. for attachment to the earlobes of a patient. An electricalconductor for application to the skin comprises a generally conicalneedle point capable of penetrating the epidermis to provide goodelectrical contact over a small area. The disclosed apparatus and methodcan be used to treat a number of disorders including appetitedisturbance; TCET administered at the appropriate time of day could beused to suppress (or enhance) appetite. U.S. Pat. No. 5,263,480 and U.S.Pat. No. 5,188,104 both to Wernicke disclose a method for treatingpatients having a compulsive eating disorder, such as compulsive eatingto excess and compulsive refusal to eat (anorexia nervosa). The methodincludes the steps of detecting a preselected event indicative of animminent need for treatment of the disorder, and applying apredetermined stimulating signal to the patient's vagus nerve (tenthcranial nerve). U.S. Pat. No. 5,084,007 discloses a method forremediating imbalances or deficiencies in neuroactive substances thatmodulate neurohumoral mechanisms. An object of the invention of the '007is to provide a method for use in, e.g. stress-related disorders such ascertain forms of obesity. The method involves the concomitantadministration of transcranial electrostimulation (TE) and a neuroactivechemical promoter, to produce a greater effect than either treatmentwould produce acting individually. U.S. Pat. No. 4,646,744 discloses amethod for treating various disorders or afflictions, e.g. stress, drugaddictions, appetite disturbances, insomnia, etc., the method includingthe transcranial application of electrical signals to the patient. U.S.Pat. No. 3,762,396 discloses a method for treating various psychosomaticailments by the application of synchronized energetic stimuli to thepatient. In particular, electric current pulses are passed through thebrain stem via electrodes attached to the back of the head and forehead.A second stimulus of electric current pulses is passed through the opticnerve via electrodes attached to the temples and forehead. Theelectrodes are mounted on a single elastic band which encircles the headof the patient, and provides electrode contact pressure.

Similarly, a number of attempts have been made to treat variousdisorders, including eating disorders, using certain drug therapies. Forexample, U.S. Pat. No. 5,554,643 discloses a series of syntheticpeptide-related compounds which are pro-drugs useful, inter alia, asantipsychotic agents and for the treatment of obesity. The '643 patentrefers to drug (amphetamine) delivery (to Sprague Dawley rats) viaintracerebral injection cannulae as part of an experiment to demonstratethe usefulness of the disclosed peptide-related compounds asantipsychotic agents, while the disclosed novel compounds themselves areadministered via intraperitoneal injection. The '643 also disclosesappetite suppressant studies in which the novel compounds areadministered intravenously through a cannulated jugular vein. In testsof anxiolytic activity exhibited by the disclosed compounds, pro-drugadministration (to mice) is performed subcutaneously, intraperitonealy,or by mouth. U.S. Pat. No. 5,523,306 and U.S. Pat. No. 5,397,788 bothalso to Horwell et al. disclose substantially the same material as the'643. U.S. Pat. No. 5,399,565 discloses novel substitutedpyrazolidinones which exhibit binding to cholecystokinin (CCK) receptorsand gastrin receptors in the brain and/or peripheral sites. Thepyrazolidinones are CCK and gastrin receptor antagonists which areuseful for, inter alia, appetite regulation. The CCK and gastrinreceptor antagonists may be administered orally, parenterally,transdermally, or as suppositories. U.S. Pat. No. 5,340,802 disclosespeptide analog type-B cholecystokinin (CCK) receptor ligands which areuseful for treating various disorders, including eating disordersrelated to appetite control. The compounds of the '802 may beadministered in a number of ways, including orally, parenterally(injectable preparations), subcutaneously, topically, and via liposomes.U.S. Pat. No. 5,262,178 discloses a method and therapeutic compositionfor the treatment of pathological disorders associated with endogenouspeptides by the administration of enkephalinase and novel forms thereof.Enkephalinase is implicated in the hydrolysis of endogenous enkephalinsin brain tissue, while the effects of enkephalins includegastrointestinal function and increasing appetite. (Administration maybe transdermal, intramuscular, intravenous, subcutaneous, intranasal,intraarticular injection, as a topical preparation for local therapy, byaerosol inhalation, by intravascular infusion, and by microparticulatedelivery systems, e.g. liposomes.) U.S. Pat. No. 5,120,713 discloses amethod for treating obese patients by administering to the patient bothan alpha-2-adrenergic agonist, e.g. clonidine, and a growth hormonereleasing peptide, e.g. growth hormone releasing hormone (GHRH), torestore or enhance growth hormone release in such patients. Typicallyclonidine is administered orally, preferably about 1 hour prior toadministering the growth hormone releasing peptide, while GHRH istypically administered by injection (i.v. or s.c.).

In previous animal studies, direct microinjections of neuropeptide Y(NPY) into various discrete hypothalamic nuclei of the rat consistentlyincreased food intake in all regions examined (Jolicoeur, F. B., et al.,“Mapping of hypothalamic sites involved in the effects of NPY on bodytemperature and food intake,” Brain Research Bulletin, 36:125–129,1995).

Previous studies have demonstrated that an electrical stimulation devicecan be safely implanted into the human hypothalamus using standardstereotactic techniques. See for example Dieckman, G, et al., “Influenceof stereotactic hypothalamy on alcohol and drug addiction”, Appl.Neurophysiol., 41:93–98, 1978; Mayanagi, Y., et al., “The posteromedialhypothalamus and pain, behavior, with special reference toendocrinological findings”, Appl. Neurophysiol. 41:223–231, 1978; Nakao,H., Emotional behavior produced by hypothalamic stimulation”, Am. J.Physiol. 194:411418, 1958; Sano, K. “Effects of stimulation anddestruction of the posterior hypothalamus in cases of behavior disordersand epilepsy”, Special topics in stereotaxis. Berlin Symposium 1970.Hippokrates Verlag Stuttgart.

Similarly, prior art studies have demonstrated that manipulation of thehuman hypothalamus may effect changes in appetite. Thus Sano observed amarked increase in appetite, resulting in weight gain, as an unintendedside effect of certain hypothalamic lesions (Sano, K. “Effects ofstimulation and destruction of the posterior hypothalamus in cases ofbehavior disorders and epilepsy”, Special topics in stereotaxis. BerlinSymposium 1970. Hippokrates Verlag Stuttgart).

Animal studies directed at determining the effects of periodichypothalamic electrical stimulation on weight gain in rats, haveprovided strong indirect evidence of the feasibility of using electricalstimulation of the hypothalamus therapeutically in obese humans todecrease body weight. For example, Bielejaw, et al., and Stenger, et al.found that periodic electrical stimulation of specific loci within thehypothalamus with a 50 Hz stimulation current reduces weight gain inrats. (Bielejaw, C., et al., “Factors that contribute to the reducedweight gain following chronic ventromedial hypothalamic stimulation”,Behavioral Brain Research 62:143–148, 1994; Stenger, J., et al., “Theeffects of chronic ventromedial hypothalamic stimulation on weight gainin rats”, Physiol. Behav. 50:1209–1213, 1991). In these animal studies,episodic periods of electrical stimulation were delivered to the rathypothalamus from a single contact electrode coupled to an externalstimulation source, as opposed to a chronic indwelling, multicontactelectrode stimulation system contemplated by Applicant for humantherapeutic use.

The above references are incorporated by reference herein whereappropriate for appropriate teachings of additional or alternativedetails, features and/or technical background.

SUMMARY OF THE INVENTION

It is therefore an object of the instant invention to provide anapparatus including an introducer tube for introducing an electrodeassembly into a specific region of a patient's brain.

It is a further object of the invention to provide an apparatus whichincludes an electrode assembly having a rigid electrode support shaftbearing at least one neuron-monitoring bipolar microelectrode.

It is a further object of the invention to provide an electrode assemblywhich includes at least one neuron-monitoring bipolar microelectrode,the electrical contacts of which are flexible.

It is a further object of the invention to provide an electrode assemblybearing at least one neuron-monitoring bipolar microelectrode, which canbe used to obtain high quality recordings of action potentials ofindividual neurons chronically over a period of a number of days.

It is a further object of the instant invention to provide an apparatuswhich includes a dual purpose electrode assembly which is used for bothmonitoring neuronal physiology and for chronic electrical stimulation ofa target cell or target tissue.

It is a further object of the instant invention to provide an apparatuswhich includes a dual purpose electrode assembly which is used for bothmonitoring neuronal physiology and for making lesions at the site of atarget cell or target tissue.

It is a further object of the invention to provide a dual purposemulticontact neuron-monitoring and lesion-producing electrode assemblyhaving a plurality of neuron-monitoring microelectrodes, andlesion-producing capability located at a plurality of sites on theelectrode assembly, the sites of lesion-producing capability having adefined location relative to the location of the microelectrodes.

It is a further object of the invention to provide a dual purposeneuron-monitoring and lesion-producing electrode assembly having aplurality of neuron-monitoring microelectrodes and an equal number ofadjacently located, spatially paired, or coincidental sites oflesion-producing capability.

It is still a further object of the invention to provide a dual purposemulticontact electrode assembly, with both neuron-monitoring andlesion-producing capability, having a magnetically tipped electrodesupport shaft for stereotactic placement of the electrode support shaftin a specific conformation within the target tissue, wherein the supportshaft is positioned under remote control by means of an externalmagnetic field applied in the vicinity of the target tissue.

It is yet a further object of the invention to provide an apparatus forperforming ablative surgery on a specific region of a patient's brain,including a magnetically tipped multicontact dual purpose electrodeassembly having the capacity to both monitor individual neurons withinthe target brain tissue and to produce lesions at the site within thetarget tissue at which neurons were monitored.

It is a further object of the instant invention to provide an apparatuswhich includes a dual purpose electrode assembly which is used for bothmonitoring neuronal physiology and for delivering therapeutic drugs tothe site of a target cell or target tissue.

It is a further object of the invention to provide a dual purposemulticontact neuron-monitoring/drug delivery electrode assembly having aplurality of neuron-monitoring microelectrodes and a plurality of sitescapable of delivering a drug located on the electrode assembly, thesites of drug delivery capability having a defined location relative tothe location of the microelectrodes.

It is a further object of the invention to provide a dual purposeneuron-monitoring/drug delivery electrode assembly having a plurality ofneuron-monitoring microelectrodes and an equal number of adjacentlylocated, spatially paired, or coincidental sites of drug deliverycapability.

It is still a further object of the invention to provide a dual purposemulticontact electrode assembly, with both neuron-monitoring and drugdelivery capability, having a magnetically tipped electrode supportshaft for stereotactic placement of the electrode support shaft in aspecific conformation within the target tissue, wherein the supportshaft is positioned under remote control by means of an externalmagnetic field applied in the vicinity of the target tissue.

It is yet a further object of the invention to provide a method fordelivering therapeutic drugs to target tissue(s) of a patient in which adual purpose multicontact neuron-monitoring/drug delivering electrodeassembly is inserted into the target tissue, at least one cell of thetarget tissue is monitored for physiologic activity usingmicroelectrodes, and subsequently, a suitable dose of a therapeutic drugmay be selectively delivered from a specific site on the electrodeassembly to the specific region of the target tissue which wasmonitored.

It is a further object of the invention to provide a method fordelivering therapeutic drugs to target tissue(s) of a patient, in whicha dual purpose multicontact neuron-monitoring/drug delivering electrodeassembly is inserted into the target tissue, the exact location andorientation of the target tissue being determined by computer assistedtomography (CT) scan and/or 3-dimensional magnetic resonance imaging(MRI).

It is yet a further object of the invention to provide a method fordelivering therapeutic drugs to target tissue(s) of a patient, in whicha dual purpose multicontact neuron-monitoring/drug delivery electrodeassembly having a magnetic tip is moved to an appropriate positionwithin the target tissue by the application of a magnetic field outsidethe patient's body part undergoing therapy.

It is still a further object of the invention to provide a dual purposeneuron-monitoring/drug delivery electrode assembly having at least oneneuron-monitoring microelectrode, and at least one drug delivery portfor the delivery of therapeutic drugs to specific, previously-monitored,sites within target tissue(s), the at least one drug delivery porthaving a defined location on the electrode assembly relative to thelocation of the microelectrodes.

It is yet a further object of the invention to provide a method forperforming ablative surgery on a specific region of a patient's brain,in which a dual purpose multicontact electrode assembly is inserted intothe target tissue, a plurality of neurons are monitored for physiologicactivity using microelectrodes, and subsequently, without moving themicroelectrodes, one or more macroelectrodes may be selectivelyactivated or energized to form lesions within the target tissue at thesite of the specific neurons which were monitored.

It is a further object of the invention to provide a method forperforming ablative surgery on a specific region of a patient's brain,in which a dual purpose multicontact electrode assembly is inserted intothe target tissue, the exact location and orientation of the targettissue being determined by computer assisted tomography (CT) scan and/or3-dimensional magnetic resonance imaging (MRI).

It is yet a further object of the invention to provide a method forperforming ablative surgery, in which a dual purpose multicontactelectrode assembly having a magnetic tip is moved to an appropriateposition within the target tissue by the application of a magnetic fieldoutside the patient's body part undergoing surgery.

Another object of the invention is to provide a prosthetic which can beplaced in a cerebral cortex to reconstitute sensor input to the brainusing microstimulation.

It is still a further object of the invention to provide a neuralprosthesis including a multicontact electrode assembly which has amagnetic tip for stereotactic placement of the electrode assembly withinauditory cortex.

It is still a further object of the invention to provide a multicontactelectrode assembly which has a magnetic tip for stereotactic placementof the electrode assembly within the target tissue by means of applyingan external magnetic field in the vicinity of the target tissue.

It is a further objective of the invention to provide a method forpositioning a neural prosthesis having a magnetic tip in an appropriateconformation within the auditory cortex.

Another object of the invention is to provide a prosthetic which can bepositioned in the brain such that an entire range of tonal frequenciesprocessed by the human brain are accessed thereby.

Another object of the invention is to provide a prosthetic which allowsa physician to physiologically test location and function of neuralprosthetic electrodes in patients undergoing surgery for medicallyintractable epilepsy.

It is still yet a further object of the invention to provide ahypothalamic obesity probe for stereotactic placement in thehypothalamus of an obesity patient and for performing electricalstimulation trials to determine the effect of electrical stimulation ofthe hypothalamus on appetite regulation.

Another object of the invention is to provide a stimulation trialshypothalamic obesity probe, wherein the obesity probe is placed in thehypothalamus of an obesity patient, and the obesity probe is used todeliver electrical discharges to specific regions of the hypothalamus inorder to determine which regions of the hypothalamus are involved inappetite regulation.

Another object of the invention is to provide a drug infusion assemblyfor microinfusing a drug into the hypothalamus of an obesity patient,the drug infusion assembly including at least one microinfusion catheterfor placement in the hypothalamus of the patient, and a macrocatheterfor housing the at least one microinfusion catheter, the macrocatheterhaving a magnetic unit to allow magnetic stereotactic manipulation ofthe catheter within the patient's brain.

Another object of the invention is to provide a method for defining anappropriate region within the hypothalamus in which to provide chronicelectrical stimulation for the treatment of an obesity patient.

Another object of the invention is to provide a method for treating anobesity patient by outputting electrical discharges into a specificregion, or specific regions, of the hypothalamus of the patient.

Another object of the invention is to provide a method for treating anobesity patient by infusion of a drug from a drug infusion assembly intospecific regions of the hypothalamus of the patient.

Another object of the invention is to provide a method for treating anobesity patient by localized infusion of a drug from at least one drugdelivery port of a microinfusion catheter into a specific region, orspecific regions, of the hypothalamus of the patient.

One feature of the invention is that it includes a penetratinglongitudinal support or electrode.

Another feature of the invention is that it can include a plurality ofelectrical contacts on the longitudinal support.

Another feature of the invention is that it includes a speech processor.

Another feature of the invention is that each electrode on the electrodesupport can separately and independently introduce electrical dischargesin the brain.

Another feature of the invention is that it is arranged along theauditory cortex.

Another feature of the invention is that it can include a flexiblemulticontact electrode support.

Another feature of the invention is that the flexible multicontactelectrode support is inserted into the brain using a rigid introducer.

Another feature of the invention is that a flat plastic plate attachedto the longitudinal support helps position the prosthetic in theauditory cortex, the flat plastic plate having a cup to receive a spherecoupled to leads which interconnect the contacts to the speechprocessor.

Still another feature of the invention is that a plurality of electrodesupport shafts, each bearing a plurality of longitudinally arrangedstimulation electrodes, can be stereotactically placed in thehypothalamus of a patient, and the clinical effects of electricalstimulation of neurons in the hypothalamus can be monitored.

Another feature of the invention is that a stimulation trialshypothalamic obesity probe includes a plurality of electrode supportshafts, each bearing a plurality of longitudinally arranged stimulationelectrodes, each of the plurality of stimulation electrodes capable ofindependently outputting electrical discharges over a variable frequencyrange from about 10 Hz to about 400 Hz.

Another feature of the invention is that a stimulation trialshypothalamic obesity probe can be stereotactically placed in a selectedregion of the hypothalamus of a patient, and the clinical effects ofelectrical stimulation of neurons by electrical discharges of variousfrequencies and from various stimulation electrodes of the hypothalamicobesity probe can be monitored in order to optimize the clinical effectsof the electrical stimulation of neurons in the hypothalamus.

Another feature of the invention is that a drug infusion assembly can bepositioned within the hypothalamus of a patient and a drug for thetreatment of obesity can be microinfused from at least one microinfusioncatheter into one or more specific sites within the hypothalamus.

Another feature of the invention is that an obesity patient can betreated for obesity using at least one microinfusion catheter to delivera drug for obesity treatment to one or more specific sites within thehypothalamus.

Another feature of the invention is that an obesity patient can betreated for obesity by implanting a chronic electrical stimulator withina specific region, or specific regions, of the hypothalamus.

One advantage of the invention is that it includes contacts which enablea deaf patient to hear even though the patient's problem is not in hisor her cochlear regions but instead is farther “down stream.”

Another advantage of the invention is that it can utilize a singleelectrode or electrical contact mounted on an electrode support.

Another advantage of the invention is that it penetrates the brain, thusrequiring a smaller, more readily tolerable current to stimulatelocalized regions of the auditory cortex, compared to the amount ofcurrent required during stimulation of the brain surface.

Another advantage of the invention is that the contacts are sufficientlyclosely arranged next to each other to provide high resolutionstimulation of the auditory cortex.

Still another advantage of the invention is that a stimulation trialshypothalamic obesity probe can be stereotactically placed in one or moreselected regions of the hypothalamus of a patient, and the clinicaleffects of electrical stimulation of the one or more selected regions ofthe hypothalamus can be monitored to determine which regions of thehypothalamus are involved in appetite regulation.

Another advantage of the invention is that a stimulation trialshypothalamic obesity probe can be stereotactically placed in one or moreselected regions of the hypothalamus of a patient, and the clinicaleffects of electrical stimulation of the one or more selected regions ofthe hypothalamus can be monitored in order to define an appropriateregion within the hypothalamus for placement of at least onemicroinfusion catheter.

Another advantage of the invention is that at least one microinfusioncatheter can be placed within a selected region of the hypothalamus anda drug for the treatment of obesity can be microinfused into one or morespecific sites within the hypothalamus.

These and other objects, advantages and features are accomplished by theprovision of a neural prosthetic device for an auditory cortex of apatient, including: a speech processor for receiving and processingaudio information and for outputting processed electrical signals; asupport arranged in the auditory cortex having a plurality of electricalcontacts independently outputting electrical discharges in accordancewith the processed electrical signals; and electrical coupling means forelectrically coupling the electrical contacts to the speech processor.

The above objects, advantages and features are further accomplished bythe neural prosthetic apparatus as above, wherein the support isarranged in the auditory cortex and the plurality of electrical contactsare arranged such that the plurality of electrical contactsapproximately tonotopically match the auditory cortex.

These and other objects, advantages and features are also accomplishedby a method of implanting the above support, including the steps of:acquiring a 3-dimensional digital image of the patient's brain andstoring the 3-dimensional digital image in a memory of a computer;digitally subtracting data from the 3-dimensional digital image to yielda modified 3-dimensional digital image which shows the orientation ofthe auditory cortex in the patient's brain; and inserting the supportinto the auditory cortex using the modified 3-dimensional digital imageas a guide.

The above and other objects, advantages and features are furtheraccomplished by the steps of: repeatedly outputting the processedelectrical signals to the plurality of electrical contacts; andadjusting orientation of the support in the auditory cortex as thepatient describes effects of the repeatedly outputting step.

These and other objects, advantages and features are accomplished by theprovision of a stimulation trials hypothalamic obesity probe forstereotactic placement in the hypothalamus of a patient, thehypothalamic obesity probe including: at least one electrode supportshaft, each of the at least one electrode support shafts having aplurality of electrical contacts, each of the plurality of electricalcontacts electrically coupled to an electrical stimulation device fortransmitting electrical signals to each of the plurality of electricalcontacts, and each of the plurality of electrical contacts capable ofindependently outputting to electrical discharges to the hypothalamus;and a macrocatheter for housing the at least one electrode supportshaft, the macrocatheter including a magnetic unit for magneticstereotactic placement of the macrocatheter to a location adjacent tothe hypothalamus.

These and other objects, advantages and features are accomplished by theprovision of a stimulation trials hypothalamic obesity probe forstereotactic placement in the hypothalamus of a patient, including: atleast one electrode support shaft, each of the at least one electrodesupport shaft having a plurality of stimulation electrodes, each of theplurality of stimulation electrodes electrically coupled to anelectrical stimulation device for transmitting electrical signals toeach of the plurality of stimulation electrodes, and each of theplurality of stimulation electrodes capable of independently outputtingelectrical discharges to the hypothalamus; and a macrocatheter forhousing the at least one electrode support shaft.

These and other objects, advantages and features are accomplished by theprovision of a stimulation trials hypothalamic obesity probe which isplaced in the hypothalamus of an obesity patient, and the obesity probeis used to determine an appropriate region of the hypothalamus in whichto position a chronic electrical stimulation device, the chronicelectrical stimulation device positioned in the hypothalamus for thesuppression of appetite of the obesity patient.

These and other objects, advantages and features are accomplished by theprovision of a drug infusion assembly for microinfusing a drug into thehypothalamus, the drug infusion assembly including: at least onemicroinfusion catheter, each of the at least one microinfusion cathetersfor placement in the hypothalamus, each of the at least onemicroinfusion catheters having a plurality of drug delivery ports, eachof the plurality of drug delivery ports for delivering a drug to aseparate site within the hypothalamus; a macrocatheter for housing theat least one microinfusion catheter; a drug delivery manifold, each ofthe at least one microinfusion catheters functionally coupled to thedrug delivery manifold; a drug supply line functionally coupled to thedrug delivery manifold; a drug reservoir/pump for retaining and pumpinga drug, the drug reservoir/pump functionally coupled to the drug supplyline; and the macrocatheter includes a magnet located at the distal endof the macrocatheter.

These and other objects, advantages and features are accomplished by theprovision of a method for treating an obesity patient by outputtingelectrical discharges from a hypothalamic obesity probe to selectedportions of the patient's hypothalamus, including the steps of a)obtaining a three dimensional digital image of the patient's brain, theimage including and showing the position of the hypothalamus; b)inserting a macrocatheter adjacent to the hypothalamus; c) inserting atleast one electrode support shaft into the hypothalamus, wherein the atleast one electrode support shaft bears a plurality of longitudinallyarranged stimulation electrodes, each of the plurality of stimulationelectrodes being capable of independent control; d) outputtingelectrical discharges from at least one of the plurality of stimulationelectrodes, thereby stimulating at least one neuron in the hypothalamus;e) monitoring the clinical effect or clinical effects of step d), inorder to determine those particular stimulation electrodes of theplurality of stimulation electrodes which will provide a clinicallyuseful effect; and f) delivering electrical discharges from thoseparticular stimulation electrodes of the plurality of stimulationelectrodes determined in step e) to provide a clinically useful effect.

These and other objects, advantages and features are accomplished by theprovision of a method for treating an obesity patient by microinfusing adrug into one or more selected portions of the hypothalamus of apatient, including the steps of: a) obtaining an image of thehypothalamus of the patient; b) inserting a drug infusion assembly intothe patient's brain adjacent to the hypothalamus, wherein the druginfusion assembly includes a macrocatheter, the macrocatheter housing atleast one microinfusion catheter, and each of the at least onemicroinfusion catheters includes a plurality of independentlycontrollable drug delivery ports; c) inserting the at least onemicroinfusion catheter into the hypothalamus; d) sequentially infusing adrug from various members of the plurality of drug delivery ports on theat least one microinfusion catheter into corresponding sites of thehypothalamus proximate the various members of the plurality of deliveryports; e) monitoring the clinical effect of step d), in order todetermine which of the various members of the plurality of drug deliveryports will provide a useful clinical result; and f) delivering a drugfrom those selected members of the plurality of delivery portsdetermined in step e) to provide a useful clinical result.

These and other objects, advantages and features are accomplished by theprovision of a method for treating an obesity patient by electricalstimulation of the hypothalamus of the patient, including the steps of:a) providing a three dimensional digital image of the patient's brain inorder to indicate the precise location of the hypothalamus; b) forming aburr hole at an appropriate location in the patient's cranium; c)inserting an introducer tube into the burr hole; d) introducing amacrocatheter into the introducer tube, wherein the macrocatheterincludes at least one electrode support shaft having a plurality ofstimulation electrodes, the plurality of stimulation electrodes arrangedlongitudinally on the at least one electrode support shaft; e) insertingthe macrocatheter in a zone of the patient's brain adjacent to thehypothalamus; f) inserting the at least one electrode support shaft intothe hypothalamus; g) electrically stimulating at least one neuron in thehypothalamus by means of electrical discharges outputted from one ormore of the plurality of stimulation electrodes; h) monitoring theclinical effect of step g) to define regions of the hypothalamus whichwill provide a desired clinical result when electrical discharges areoutputted thereto; and i) outputting electrical discharges to regions ofthe hypothalamus defined in step h).

These and other objects, advantages and features are accomplished by theprovision of a method for treating an obesity patient by chronicelectrical stimulation of the hypothalamus of the patient, including thesteps of: a) obtaining a three dimensional digital image of a patient'sbrain showing the location of the hypothalamus; b) inserting amacrocatheter into a zone of the patient's brain adjacent to thehypothalamus, wherein the macrocatheter houses at least one electrodesupport shaft, and each of the at least one electrode support shafts hasa plurality of stimulation electrodes, and each of the plurality ofstimulation electrodes is capable of independently outputting electricaldischarges of various frequencies; c) inserting the at least oneelectrode support shaft into the hypothalamus of the patient; d)delivering electrical discharges of various frequencies from a first setof the plurality of stimulation electrodes to a first set of neuronswithin the hypothalamus; e) delivering electrical discharges of variousfrequencies from at least one further set of the plurality ofstimulation electrodes to at least one further set of neurons within thehypothalamus; f) monitoring the clinical effects of steps d) and e) onappetite regulation by the patient, in order to determine the clinicaleffects of various combinations of electrical dischargefrequency/location of stimulation electrodes; g) optimizing theelectrical discharges delivered to the neurons within the hypothalamus,according to steps d) and e), to provide optimum appetite regulation bythe patient; and h) programming the hypothalamic obesity probe forchronic delivery of electrical discharges of defined frequency and atspecific locations within the hypothalamus, as determined in step g), toprovide optimum appetite regulation by the patient.

These and other objects, advantages and features are accomplished by theprovision of a method for chronic electrical stimulation of thehypothalamus of an obesity patient, including the steps of: obtaining athree dimensional image of a patient's brain, the three dimensionalimage showing the location of the hypothalamus; inserting amacrocatheter into a zone of the patient's brain, wherein the zone isadjacent to the hypothalamus, wherein the macrocatheter houses at leastone electrode support shaft, each of the at least one electrode supportshafts having a plurality of stimulation electrodes, and each of theplurality of stimulation electrodes capable of independently outputtingelectrical discharges, the electrical discharges of low frequency or ofhigh frequency; inserting the at least one electrode support shaft intoa selected first region of the hypothalamus; stimulating, by means ofelectrical discharges outputted from the plurality of stimulationelectrodes, neurons in the selected first region of the hypothalamus;and monitoring the clinical effects of the stimulating neurons step.

These and other objects, advantages and features are accomplished by theprovision of a method for treating an obesity patient by placing achronic electrical stimulator into the hypothalamus of the patient,including the steps of: a) obtaining a three dimensional image of apatient's brain, the three dimensional image showing the location of thehypothalamus; b) inserting a macrocatheter into a zone of the patient'sbrain, wherein the zone is adjacent to the hypothalamus, wherein themacrocatheter houses at least one electrode support shaft, each of theat least one electrode support shafts having a plurality of stimulationelectrodes, and each of the plurality of stimulation electrodes capableof independently outputting electrical discharges, the electricaldischarges of low frequency or of high frequency; c) inserting the atleast one electrode support shaft into a selected first region of thehypothalamus; d) stimulating, by means of electrical dischargesoutputted from the plurality of stimulation electrodes, neurons in theselected first region of the hypothalamus; e) monitoring the clinicaleffects of step d); f) after step e), reinserting the at least oneelectrode support shaft into a selected additional region of thehypothalamus; g) stimulating, by means of electrical dischargesoutputted from the plurality of stimulation electrodes, neurons in theselected additional region of the hypothalamus; h) monitoring clinicaleffects of step g); i) repeating steps f) through h) until asatisfactory clinical effect is obtained; j) pre-programming the chronicelectrical stimulator so as to duplicate the satisfactory clinicaleffect as obtained in step i); and implanting the preprogrammed chronicelectrical stimulator in an appropriate region of the hypothalamus.

These and other objects, advantages and features are accomplished by theprovision of a method for treating an obesity patient by infusion of adrug from a drug infusion assembly into the hypothalamus of the patient,the method including the steps of: a) obtaining a three dimensionalimage of a patient's brain, the three dimensional image showing thelocation of the hypothalamus; b) inserting a macrocatheter into a zoneof the patient's brain, wherein the zone is adjacent to thehypothalamus, wherein the macrocatheter houses at least onemicroinfusion catheter, each of the at least one microinfusion cathetershaving a plurality of drug delivery ports, and each of the plurality ofdrug delivery ports capable of independently outputting a drug, the drugcapable of activating or deactivating neurons in one or more regions ofthe hypothalamus; c) inserting the at least one microinfusion catheterinto a selected first region of the hypothalamus; d) infusing a quantityof a drug from at least one of the plurality of drug delivery ports toat least one neuron of the selected first region of the hypothalamus;and e) monitoring clinical effects of step d).

These and other objects, advantages and features are accomplished by theprovision of a method for treating an obesity patient by chronicelectrical stimulation of the hypothalamus of the patient, the methodincluding the steps of: a) obtaining a three dimensional digital imageof a patient's brain showing the location of the hypothalamus; b)inserting a macrocatheter into a zone of the patient's brain adjacent tothe hypothalamus, the macrocatheter housing at least one electrodesupport shaft, each of the at least one electrode support shafts havinga plurality of stimulation electrodes, and each of the plurality ofstimulation electrodes capable of independently outputting electricaldischarges of various frequencies; c) inserting the at least oneelectrode support shaft into the hypothalamus; d) delivering electricaldischarges of various frequencies from a first set of the plurality ofstimulation electrodes to a first set of neurons within thehypothalamus; e) delivering electrical discharges of various frequenciesfrom at least one further set of the plurality of stimulation electrodesto at least one further set of neurons within the hypothalamus; f)monitoring the clinical effects of steps d) and e) on appetiteregulation by the patient; g) based on steps d) through f), optimizingthe electrical discharges delivered to the neurons within thehypothalamus for optimum appetite regulation by the patient; h) based onstep g), pre-programming a chronic electrical stimulator for optimumclinical effectiveness in the patient; and i) implanting thepre-programmed chronic electrical stimulator in the hypothalamus of thepatient.

One feature of the invention is that it can include a penetratinglongitudinal support shaft bearing a single microelectrode formonitoring physiologic activity of a cell.

Another feature of the invention is that it can include a penetratinglongitudinal support shaft bearing multiple microelectrodes formonitoring physiologic activity.

Another feature of the invention is that each microelectrode formonitoring physiologic activity can be bipolar.

Another feature of the invention is that each neuron-monitoringmicroelectrode of the electrode assembly can independently monitor thephysiological activity of the neuron(s) with which it makes contact.

Another feature of the invention is that each lesion-producingmacroelectrode of the electrode assembly can be independently energizedto produce a localized lesion.

Another feature of the invention is that the electrode support shaft ofthe electrode assembly can be rigid.

Another feature of the invention is that the electrode support shaft ofthe electrode assembly can be flexible.

Another feature of the invention is that it can include a magnet at itsdistal end.

Another feature of the invention is that the flexible support shaft canbe positioned generally along the long axis of the globus pallidus.

Another feature of the invention is that the multicontact electrodesupport shaft is introduced into the brain using a stereotacticallyinserted introducer tube.

One advantage of the invention is that it can function with a singleelectrode support shaft.

Another advantage of the invention is that it allows theneuron-monitoring and lesion-producing functions of prior artpallidotomy to be performed by the same electrode assembly.

Another advantage of the invention is that the microelectrode andmacroelectrode contacts are sufficiently small and closely arranged onthe electrode support shaft to enable high resolution monitoring andinactivation of the target tissue.

Another advantage of the invention is that it reduces the chances forerror in placement of electrodes during surgical procedures byeliminating the need to use separate neuron-monitoring and lesion-makingelectrode assemblies.

Another advantage of the invention is that it allows the monitoring of aplurality of neurons and the subsequent production of a plurality oflesions following a single placement of the electrode support shaftwithin the target tissue.

Another advantage of the invention is that the neuron-monitoringmicroelectrodes and lesion-producing macroelectrodes are sufficientlysmall and closely arranged next to each other to enable a high degree ofspatial correlation between neuron monitoring and neuron inactivationfunctions.

Another advantage of the invention is that the electrode support shaftcan be retrieved from a given position within the brain to theintroducer tube by exerting a force on a tether line.

Yet a further advantage of the invention is that the magnetically tippedelectrode support shaft can be positioned in a desired spatialorientation within the brain by changing the magnitude and direction ofmagnetic forces which urge the electrode support shaft forwards.

These and other objects, advantages and features are accomplished by theprovision of an apparatus for performing surgery on a patient,including: an electrode assembly including an electrode support shaftbearing a plurality of spatially paired or coincidental microelectrodesand macroelectrodes, and an introducer tube for introducing theelectrode support shaft into the patient. The electrode assembly alsoincludes a tether line for retrieving the electrode assembly from thetarget tissue.

These and other objects, advantages and features are accomplished by amethod of performing surgery on a patient, including the steps of:introducing the distal end of the electrode support shaft into thetarget tissue, monitoring a plurality of neurons therein for theirphysiologic response, and subsequently selectively energizing one ormore spatially paired or coincidental lesion-producing macroelectrodesaccording to the response recorded from the plurality ofmicroelectrodes.

These and other objects, advantages and features are accomplished by amethod of performing surgery on a patient, including the steps of:stereotactically inserting an introducer tube into the brain of apatient such that the distal end of the tube is positioned close to thetarget tissue, introducing an electrode assembly into the introducertube, the electrode assembly including an electrode support shaftbearing a magnetic tip responsive to an external magnetic field, drivingthe magnetic tip of the electrode assembly through a defined trajectorywithin the globus pallidus, monitoring the physiological activity of atleast one neuron within the globus pallidus, optionally, according tothe monitoring of the physiological activity, inactivating the at leastone neuron by activating the at least one macroelectrodes.

These and other objects, advantages and features are accomplished by theprovision of an apparatus for performing pallidotomy on a patient,including: an electrode assembly having a magnetically tipped, flexibleelectrode support shaft bearing a plurality of spatially pairedmicroelectrodes and macroelectrodes, respectively for monitoring andinactivating specific neurons or groups of neurons, and an introducertube for introducing the electrode support shaft into the patient. Theelectrode assembly also includes a tether line for retrieving theelectrode assembly from the target tissue. The electrode assembly maythen be repositioned in the home position within the introducer tube.These and other objects, advantages and features are accomplished by amethod of performing a pallidotomy on a patient including the steps of:introducing the distal end of the electrode support shaft into theglobus pallidus, monitoring a plurality of neurons therein for theirphysiologic response using a plurality of neuron-monitoringmicroelectrodes, and subsequently selectively energizing one or morespatially paired lesion-producing macroelectrodes according to theresponse recorded from the plurality of microelectrodes.

These and other objects, advantages and features are accomplished by amethod of performing pallidotomy on a patient, including the steps of:stereotactically inserting an introducer tube into the brain of apatient such that the distal end of the tube is positioned close to thelateral globus pallidus; introducing an electrode assembly into theintroducer tube, the electrode assembly including an electrode supportshaft, the electrode support shaft having a magnetic distal endresponsive to an external magnetic field and further bearing at leastone neuron-monitoring microelectrode and at least one lesion-producingmacroelectrode spatially paired with the at least one microelectrode;driving, by the application of an external magnetic field, the magneticend of the electrode assembly through a defined trajectory within theglobus pallidus; monitoring the physiological activity of at least oneneuron with the at least one microelectrode; optionally, according tothe monitoring of the physiological activity, inactivating the at leastone neuron by applying lesion-forming energy to the at least one neuronvia the at least one macroelectrode; and assessing the patient'sresponse to the above steps.

These and other objects, advantages and features are accomplished by amethod of making a dual purpose multicontact electrode assembly capableof monitoring and inactivating neurons, including the steps of:arranging a plurality of electrical contacts along the longitudinal axisof an electrode support shaft, and coupling each of the electricalcontacts to at least one strand of electrically conductive material,whereby a suitable electric current may be conducted to or from each ofthe electrical contacts.

These and other objects, advantages and features are accomplished by amethod of making a dual purpose multicontact electrode assembly,including the steps of: providing an electrode support shaft having adistal end and a proximal end, positioning a plurality ofneuron-monitoring microelectrodes along the distal end of the electrodesupport shaft, and positioning each one of a plurality oflesion-producing macroelectrodes adjacent to each one of the pluralityof microelectrodes, and affixing a magnet, responsive to an appliedexternal magnetic field, to the distal end of the support shaft.

These and other objects, advantages and features are accomplished by amethod of making an introducer tube, including the steps of: providing acylinder, rigidly attaching coaxially a conical neck to one end of thecylinder, the conical neck having a free end and the diameter of theconical neck having the same diameter as the cylinder at the point ofjuncture, the diameter of the conical neck increasing in the directionaway from the cylinder, rigidly attaching coaxially a cylindrical endpiece to the free end of the conical neck, the end piece having the samediameter as the free end of the conical neck, and providing sealingmeans for sealing the cylindrical end piece.

These and other objects, advantages and features are accomplished byprovision of an introducer tube for introducing a device into the bodyof a patient, including: a cylindrical portion, a conical neck portioncontinuous with the cylindrical portion, a short cylindrical end piececontinuous with the conical neck portion, and sealing means for sealingthe proximal end of the introducer tube.

These and other objects, advantages and features are accomplished byprovision of an apparatus for selectively inactivating neurons in atarget tissue, including: an electrode support shaft, at least onelesion-producing macroelectrode arranged on the support shaft, and atleast one neuron-monitoring microelectrode arranged on the supportshaft, each one of the at least one microelectrodes having a definedlocation on the support shaft relative to the location of the at leastone macroelectrode.

These and other objects, advantages and features are accomplished byprovision of an apparatus including: a support shaft, at least onelesion-producing macroelectrode arranged along the support shaft forproducing a lesion, and multiple neuron-monitoring microelectrodesarranged along the support shaft having a defined relative location onthe shaft with respect to the at least one lesion-producingmacroelectrode, the multiple neuron-monitoring microelectrodesmonitoring neuronal activity and outputting signals which are used todetermine whether to energize the at least one lesion-producingmacroelectrode to produce the lesion.

These and other objects, advantages and features are accomplished byprovision of an apparatus for making one or more lesions in a brain,including: an electrode support shaft, at least one lesion-producingmacroelectrode disposed on the support shaft, and a fluid-coatedintroducer tube for introducing the support shaft into the brain,thereby allowing the lesion-producing macroelectrode to make the one ormore lesions in the brain.

These and other objects, advantages and features are accomplished byprovision of an apparatus, including: a flexible electrode assemblyincluding an electrode support shaft, the support shaft having amagnetic tip which is responsive to an external magnetic field, one ormore lesion-producing macroelectrodes arranged along the support shaft,an introducer tube for introducing the support shaft into a brain, andmultiple neuron-monitoring microelectrodes arranged along the supportshaft having a defined location on the support shaft relative to the oneor more lesion-producing electrodes, the multiple neuron-monitoringmicroelectrodes monitoring neuronal activity and outputting signalswhich are used to determine whether to energize the one or morelesion-producing macroelectrodes.

These and other objects, advantages and features are accomplished byprovision of an apparatus for producing one or more lesions at one ormore locations in a globus pallidus of a human brain, including: aflexible electrode support shaft, a plurality of lesion-producingmacroelectrodes arranged along the support shaft, and a plurality ofneuron-monitoring microelectrodes arranged along the support shaft foroutputting neuron activity signals, wherein the support shaft is drapedalong the globus pallidus and selective ones of the lesion-producingcontacts are energized, in accordance with the neuron activity signals,to produce the at least one lesion in the globus pallidus.

These and other objects, advantages and features are accomplished byprovision of an apparatus for delivering one or more therapeutic drugsto target tissue of a brain, including: a support shaft, at least onedrug delivery site capable of delivering a therapeutic drug arrangedalong the support shaft, and multiple neuron-monitoring microelectrodesarranged along the support shaft having a defined relative location onthe shaft with respect to the at least one drug delivery site, themultiple neuron-monitoring microelectrodes monitoring neuronal activityand outputting signals which are used to determine whether to deliver atherapeutic drug from the at least one drug delivery site to the targettissue.

These and other objects, advantages and features are accomplished by amethod of =delivering one or more therapeutic drugs to specificlocations within the brain of a patient, including the steps of:stereotactically inserting an introducer tube into the brain of apatient such that the distal end of the tube is positioned close to thetarget tissue; introducing an electrode assembly into the introducertube, the electrode assembly including an electrode support shaft, theelectrode support shaft bearing a magnetic tip responsive to an externalmagnetic field and further bearing at least one neuron-monitoringmicroelectrode and at least one drug delivery site capable of deliveringa measured dose of a therapeutic drug, the at least one drug deliverysite being spatially paired with the at least one microelectrode;moving, by the application of an external magnetic field, the magnetictip of the electrode assembly to a defined location within the targettissue; monitoring the physiological activity of at least one neuronwith the at least one microelectrode; and, optionally according to themonitoring of the physiological activity, delivering a measured dose ofa therapeutic drug from the at least one drug delivery site.

These and other objects, advantages and features are accomplished byprovision of a neural prosthetic device for a auditory cortex of apatient, the neural prosthetic device connected to a speech processorfor receiving and processing audio information and for outputtingprocessed electrical signals, and electrical coupling means forelectrically coupling the plurality of electrical contacts to the speechprocessor.

These and other objects, advantages and features are accomplished by amethod of implanting the support of the paragraph immediately abovehaving a plurality of electrical contacts, including the steps of:acquiring a 3-dimensional digital image of the patient's brain andstoring the 3-dimensional digital image in a memory of a computer,digitally subtracting data from the 3-dimensional digital image to yielda modified 3 dimensional digital image which shows the orientation ofthe auditory cortex in the patient's brain, inserting the support intothe auditory cortex using the modified 3 dimensional digital image as aguide, repeatedly outputting processed electrical signals to theplurality of electrical contacts, and adjusting the orientation of thesupport in the auditory cortex, according to the patient's response toat least some of the processed electrical signals, the orientation ofthe support being controlled by adjustment of an applied externalmagnetic field.

These and other objects, advantages and features are accomplished byprovision of an apparatus for selectively inactivating cells in a targettissue, including: an electrode support shaft, at least onecell-monitoring microelectrode arranged on the support shaft, and atleast one lesion-producing macroelectrode arranged on the support shaft,each one of the at least one macroelectrode having a defined location onthe support shaft relative to the location of the at least onemicroelectrode.

These and other objects, advantages and features of the presentinvention will become more apparent from the following description ofembodiments thereof, taken in conjunction with the accompanyingdrawings.

Additional advantages, objects, and features of the invention will beset forth in part in the description which follows and in part willbecome apparent to those having ordinary skill in the art uponexamination of the following or may be learned from practice of theinvention. The objects and advantages of the invention may be realizedand attained as particularly pointed out in the appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will be described in detail with reference to thefollowing drawings in which like reference numerals refer to likeelements wherein:

FIGS. 1A and 1B show the orientation of a patient's auditory cortex inrelation to the patient's cochlea and cochlear nucleus.

FIG. 2 shows a human cerebral cortex neural prosthetic.

FIG. 3A shows a side view of a plane A which intersects a coronalsection with a Sylvian fissure exposed, and FIGS. 3B and 3C show thecoronal section before and after tissue is digitally “peeled off” theSylvian fissure.

FIG. 4 shows a neural prosthetic with a support having electricalcontacts and its speech processor.

FIG. 5 shows a prosthetic which includes two longitudinal supportsaccording to another embodiment of the invention.

FIG. 6 shows a prosthetic according to yet another embodiment of theinvention.

FIG. 7A shows the prosthetic of FIG. 6 as looking down on the patient'sbrain surface, FIG. 7B shows a closer view of a stopping piece with acup and a lid, and FIG. 7C corresponds to FIG. 7A with the supportinserted.

FIG. 8 shows a magnetically tipped multicontact neural prosthesis.

FIGS. 9A, 9B and 9C illustrate three different embodiments of anelectrode support shaft.

FIG. 10 shows an electrode support shaft bearing a plurality of bipolarneuron-monitoring microelectrode positioned adjacent to a plurality ofneuron-inactivating sites.

FIGS. 11A and 11B show details of an embodiment of a dual purposeelectrode assembly bearing bipolar microelectrodes, in which the pair ofelectrical contacts of the microelectrodes are closely juxtaposed, andare positioned coincidental with, and external to, the macroelectrodes.

FIG. 12A shows (arrows) the approximate location and orientation, grossmorphology, and relative size of the globus pallidus.

FIG. 12B shows (arrow) the approximate location and relative size of thethalamus.

FIG. 12C shows the parallel linear trajectories of electrode assemblies,according to prior art pallidotomy.

FIGS. 13A–13C show apparatus for performing magnetic stereotacticsurgery. FIG. 13A shows an introducer tube positioned within thepatient's skull pointing generally in the direction of the globuspallidus. FIG. 13B shows the electrode assembly ex situ. FIG. 13C showsthe electrode assembly within the introducer tube with the sealing capunattached.

FIG. 14 shows a general view of the introducer tube in cross section.

FIG. 15 shows a more detailed view of the proximal end of the introducertube with the electrode assembly positioned therein, and the sealing capunattached.

FIG. 16 shows a more detailed view of the proximal end of the introducertube with the sealing cap attached.

FIG. 17 shows the electrode support shaft positioned within the globuspallidus, together with a magnified view of a microelectrode and amacroelectrode.

FIG. 18 depicts the movement of the magnetically tipped electrodeassembly in the direction away from the introducer tube towards the apexof the globus pallidus.

FIG. 19 shows steps in performing magnetic pallidotomy using a dualpurpose multicontact electrode assembly.

FIG. 20 depicts the tether line of the electrode assembly being pulledupwards and the electrode assembly returning to the introducer tube fromthe globus pallidus.

FIG. 21 shows steps in making a dual purpose multicontact electrodeassembly useful in performing magnetic stereotactic surgery.

FIG. 22 shows steps in making an introducer tube, according to theinvention, for introducing an electrode assembly into a patient.

FIG. 23 shows an electrode support shaft of a dual purpose electrodeassembly, capable of both monitoring individual neurons and delivering achemical agent to a specific site within a patient's brain.

FIG. 24 shows steps in making a dual purpose multicontact electrodeassembly capable of both monitoring physiological activity at theindividual cell or tissue level, and delivering a chemical agent to aspecific site within a patient's tissues.

FIG. 25 shows a dual purpose neuron-monitoring/drug delivery electrodeassembly, bearing a plurality of multipolar neuron-monitoring electrodesand a plurality of drug delivery ports.

FIGS. 26A and 26B are cross-sectional views of a dual purposeneuron-monitoring/drug delivery electrode assembly at two differentpositions along its longitudinal axis showing four (26A) and three (26B)drug delivery supply lines, respectively, located within the electrodesupport shaft.

FIG. 27A shows a perspective view of a hypothalamic obesity probe forperforming electrical stimulation trials of specific regions of thehypothalamus, according to one embodiment of the invention;

FIG. 27B shows a perspective view of a hypothalamic obesity probeincluding a macrocatheter having a magnetic tip, according to anotherembodiment of the invention;

FIGS. 28A and 28B show cross-sectional views of an electrode supportshaft having monopolar electrodes, and of an electrode support shafthaving bipolar electrodes, respectively, according to other embodimentsof the invention;

FIG. 29A shows a perspective view of a hypothalamic drug infusionassembly, according to another embodiment of the invention;

FIG. 29B shows a perspective view of a hypothalamic drug infusionassembly, including a macrocatheter having a magnetic tip, according toanother embodiment of the invention;

FIG. 30 shows a perspective view of the distal end of the macrocatheterof a hypothalamic drug infusion assembly, showing microinfusioncatheters protruding therefrom, according to another embodiment of theinvention;

FIG. 31 schematically summarizes steps involved in a method forpositioning a chronic electrical stimulator in the hypothalamus of apatient, according to another embodiment of the invention;

FIG. 32 is a schematic representation of steps involved in a method fortreating an obesity patient by placing a chronic electrical stimulatorin the hypothalamus of the patient, according to another embodiment ofthe invention;

FIG. 33 schematically summarizes steps involved in a method formicroinfusing a drug from at least one microinfusion catheter into thehypothalamus of a patient, according to another embodiment of theinvention;

FIG. 34 is a schematic representation of steps involved in a method fortreating an obesity patient by microinfusing a drug from at least onemicroinfusion catheter into the hypothalamus of the patient, accordingto another embodiment of the invention;

FIG. 35A is a schematic representation of steps involved in a method fortreating an obesity patient by electrical stimulation of thehypothalamus of the patient, according to a preferred embodiment of theinvention; FIG. 35B is a schematic representation of steps involved in amethod for treating an obesity patient by microinfusing a drug from atleast one microinfusion catheter into the hypothalamus of the patient,according to another embodiment of the invention; and FIG. 35C is aschematic representation of steps involved in a method for treating anobesity patient by microinfusing a drug from at least one microinfusioncatheter into the hypothalamus of the patient, according to yet anotherembodiment of the invention;

FIG. 36A schematically shows steps involved in a method for treating anobesity patient by chronic electrical stimulation of the hypothalamus ofthe patient by implantation in the hypothalamus of a programmablehypothalamic obesity probe, according to a preferred embodiment of theinvention; FIG. 36B schematically shows steps involved in a method fortreating an obesity patient by chronic electrical stimulation of thehypothalamus of the patient by implantation in the hypothalamus of apre-programmed chronic electrical stimulator, according to anotherembodiment of the invention.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

There now follows a description of a neural prosthesis apparatus, underthe invention, as well as methods of using the same. There then followsa description of apparatus and methods for performing stereotacticmanipulations, including magnetic surgery and targeted drug delivery,according to the invention. Subsequent thereto there follows adescription of a hypothalamic obesity probe apparatus and methods forusing the same for treatment of obesity in a patient, and a descriptionof a hypothalamic drug microinfusion assembly and methods of using thesame for treating an obesity patient.

Neural Prosthesis

Advanced imaging combined with an intraoperative stereotactic system nowenable placement of penetrating electrodes into auditory cortex duringroutine epilepsy surgery without dissection of the Sylvian fissure.

Primary auditory cortex 150 in FIGS. 1A and 1B is tonotopicallyorganized, meaning stimulation in different areas is likely to cause thepatient to perceive different tones. These tones form the buildingblocks of complex sound phenomena such as speech. Tonotopic organizationis a fundamental characteristic of the cochlea and cochlear nucleus aswell, as discussed above. Primary auditory cortex 150, however, has itstonotopic map stretched across a larger volume of tissue (greater thattwice the volume of cochlear nucleus 116). Greater tissue volume enablesplacement of a greater number of electrical contacts for a giventonotopic zone. This results in increased signal resolution and improvedclarity of auditory sensation. Finally, because of anatomicaldifferences, primary auditory cortex 150 can accommodate penetratingelectrode arrays which cannot be safely placed into the cochlearnucleus.

FIG. 2 shows a human cerebral cortex neural prosthetic 200 according toone embodiment of the invention. Prosthetic 200 has a first end 206 aand a second end 206 b which is blunt or smoothly curved. Prosthetic 200has electrical contacts 220 along a longitudinal support 226. Support226 can be anywhere from several millimeters long to several centimeterslong. Electrical contacts 220 are small metal pads which can beseparately and independently electrically charged via respective wires232 available at first end 206 a. Wires 232 have leads 238 which arecoupled to a speech processor (not shown). Electrical contacts 220 arespaced approximately 10 micrometers to several millimeters apart andpreferably approximately 50 to 150 micrometers apart. Application of avoltage to contacts 220 near first end 206 a results in stimulating low(or high—to be determined by questioning the patient) tones in primaryauditory cortex 150 (see FIGS. 1A and 1B), whereas application of avoltage to contacts 220 near second end 206 b results in stimulation ofhigh (or low) tones in primary auditory cortex 150.

Longitudinal support 226 can be rigid or flexible. Prosthetic 200 may beintroduced into a patient's brain via a rigid introducer, andsubsequently electrical contacts 220 are exposed to primary auditorycortex 150. Support 226 can be one of the probes shown in FIGS. 3–5 in“Possible Multichannel Recording and Stimulating Electrode Arrays: ACatalog of Available Designs” by the Center for Integrated Sensors andCircuits, University of Michigan Ann Arbor, Mich., the contents of whichare incorporated herein by reference. Alternative electrodes such asDepthalon Depth Electrodes and interconnection cables from PMTCorporation 1500 Park Road, Chanhassen, Minn., 55317 could also be usedas support 226 and electrical couplers between contacts 220 and a speechprocessor (410 in FIG. 4).

Electrical contacts 220 must operate as high impedance (megohms)contacts as opposed to low impedance (a few ohms to several thousandohms) contacts. This makes it possible to output a greater potential forthe contacts while outputting a small (a few microamperes as opposed toa few milliamperes) current. This also localizes the potentials appliedto the patient's auditory cortex to approximately a few hundredmicrometers. The localization of applied electric charges corresponds tothe tonotopic spacing of nerve cell pairs.

Prosthetic 200 is arranged along a longitudinal direction of primaryauditory cortex 150. However, primary auditory cortex 150 is located inthe transverse temporal gyro and is buried deep within the Sylvianfissure. Consequently, its location cannot be determined simply bylooking at an exposed surface of the brain. Therefore, MRI imagingtechniques must be employed to reveal the exact orientation of primaryauditory cortex 150.

A single coronal image of an individual's brain cannot reveal the exactorientation of primary auditory cortex 150. Instead, a series of imagesmust be obtained and a resulting 3-dimensional MRI image constructed.Once such an image is constructed, the digital data making up that imagecan be transformed to provide a view of the Sylvian fissure. This inturn exposes primary auditory cortex 150 as a mound-like hump. That is,tissue on top of the digital image can be “peeled off” to expose theSylvian fissure and consequently primary auditory cortex 150 “pops out”of the image. This process is described in “Three-dimensional In VivoMapping of Brain Lesions in Humans”, by Hanna Damasio, MD, RandallFrank, the contents of which are incorporated herein by reference.

FIG. 3A shows a side view of a plane A which intersects a coronalsection 310 as well as a view of coronal section 310 with Sylvianfissure 316 exposed. FIGS. 3B and 3C show coronal section 310 before andafter tissue is digitally “peeled off” to expose primary auditory cortex150. One or more resulting mounds 320 is revealed in FIG. 3C and thismound corresponds to primary auditory cortex 150 of FIG. 1B. Mound 320does not appear until after tissue on the underside of Sylvian fissure316 is reconstructed to provide the 3-dimensional image.

Once the exact location and orientation of mound 320 and consequentlyprimary auditory cortex 150 have been determined using these3-dimensional MRI image processing techniques, the actual primaryauditory cortex 150 can be surgically exposed and prosthetic 200 can beaccurately inserted into primary auditory cortex 150. FIG. 4 showsprosthetic 200 just prior to insertion into primary auditory cortex 150.In addition, FIG. 4 shows a speech processor 410 coupled to leads 238via coupling cable 414. Examples of speech processors for speechprocessor 410 include Nucleus Device made by Cochlear Corporation.Speech processor 410 can be miniaturized and placed directly above ear416 in the patient's mastoid. FIG. 4 also shows additional diagnosticequipment including an oscilloscope 420 coupled to prosthetic 200 viacable 424.

FIG. 5 shows a prosthetic 510 which includes two longitudinal supports226 a and 226 b according to another embodiment of the invention.Although two supports are shown, three or more such supports could beused. Longitudinal support 226 a has wires 232 a with correspondingleads 238 a and longitudinal support 226 b has wires 232 b and leads 238b. Leads 238 a and 238 b are again connected to speech processor 410 asin FIG. 4. In addition, scope 420 can be used to observe signals outputto longitudinal support 226 a and 226 b.

FIG. 6 shows a prosthetic 610 according to yet another embodiment of theinvention. In particular, FIG. 6 shows longitudinal support rod 226 withfirst end 606 a and second end 606 b. End 606 a is arranged in theregion of primary auditory cortex 150 with low tones (or high tones aspreviously discussed) and second end 606 b is arranged in the region ofprimary auditory cortex 150 with high (or low) tones in a manner similarto first end 206 a and second end 206 b of FIG. 2. Here, however,longitudinal support 226 has a sphere 616 which is stopped by a stoppingpiece 614. This enables the physician to insert longitudinal support 226at a wide range of angles and yet secure prosthetic 610 oncelongitudinal support 226 has been inserted.

FIG. 7A shows prosthetic 610 of FIG. 6 as looking down on the patient'sbrain surface 704. FIG. 7B shows a closer view of stopping piece 614with a cup 708 and a lid 714 with a notch 716 for passing leads 232.FIG. 7C corresponds to FIG. 7A with support 226 inserted into surface704 and sphere 616 resting in cup 708. FIG. 7C also shows lid 714covering sphere 616 with leads 232 extending out of notch 716.

FIG. 8 shows a multicontact electrode apparatus 200 according to anotherembodiment of the invention, in which longitudinal support 226 isequipped with a magnetic tip 133 at its distal end 206 b. The attributeof a magnetic tip allows for the introduction and directed movement ofthe prosthesis to the target tissue by the application of an externalmagnetic field, as described herein in connection with the disclosedapparatus for performing magnetic pallidotomy. Furthermore, the preciselocation of a magnetically tipped neural prosthesis, which haspreviously been inserted following 3-dimensional MRI imaging andsurgical exposure of the auditory cortex, may be fine tuned by theapplication of a suitable external magnetic field (G. T. Gillies, etal., “Magnetic Manipulation Instrumentation for Medical PhysicsResearch,” Rev. Sci. Instrum., 65, 533–562 (1994)). In the latter case,the magnitude and direction of the applied magnetic field may be changedin response to the patient's auditory sensations following electricalstimulation of the auditory cortex.

Stereotactic Surgical Electrode Assembly

While all cells maintain an electrical potential across their membranes,nerve cells (neurons) are highly specialized in using membranepotentials (action potentials) to transmit signals from one part of thebody to another. The action potential of a neuron represents a transientdepolarization of its membrane over a period of a few milliseconds.Action potentials, in turn, have proved to be valuable indicators of thephysiological status and functionality of those neurons. For example, instereotactic pallidotomy the action potential of a neuron is used as thebasis for determining whether to make a lesion at the site of theparticular neuron.

Monopolar microelectrodes of the prior art comprise stiff wires whichare electrically insulated except for a relatively short, sharpened tip.By keeping the length of the uninsulated tip short, an electrode with ahigh impedance (>1 megaohms) is obtained. A higher impedancemicroelectrode allows for a more precise measurement of actionpotentials relative to ground (using such prior art microelectrodes,typically the entire body of the patient is grounded). In contrast,electrodes with a larger area of exposed (uninsulated) surface arecharacterized by a lower impedance (a few to <1 megaohms). Consequently,larger electrodes with lower impedances ordinarily record voltagetransients (field potentials) associated with larger volumes of tissue;but are unable to record action potentials from individual cells.

In accordance with an embodiment of this invention, it has now beendiscovered that action potentials can be accurately recorded fromindividual neurons using electrodes with a relatively large exposedsurface area, and a relatively low impedance. Namely, action potentialsof individual cells can be recorded using a microelectrode including anovel multipolar contact array. In a preferred embodiment, eachmicroelectrode includes a pair of contacts (corresponding to a bipolarcontact) in close juxtaposition, which are coupled to at least onedifferential amplifier (Bak Electronics, Germantown, Md.), anddifferential recordings are made from one contact relative to the other(instead of relative to patient ground as in the prior art). In anotherembodiment, each microelectrode may comprise tripolar contact arrays(stereotrodes, B. L. McNaughton, et al., “The stereotrode: a newtechnique for simultaneous isolation of several single units in thecentral nervous system from multiple unit recordings,” J. Neurosci.Methods, 8:391–397, 1983.)

Dual purpose electrode assemblies bearing neuron-monitoring electrodes,according to the invention, are useful in carrying out a range ofmedical procedures. As will be apparent to the skilled artisan,electrode assemblies of the instant invention are particularly usefulfor performing various stereotactic procedures on the brain. Suchstereotactic procedures include various surgical procedures on specificregions of brain tissue, including stereotactic pallidotomy andstereotactic thalamotomy. Electrode assemblies under the invention mayalso be used for chronically inactivating a previously-monitored,specific region of a patient's brain tissue, without forming a lesiontherein. In another embodiment, electrode assemblies of the instantinvention are also useful in delivering one or more chemical agents to apreviously-monitored, specific region of a patient's tissues. Suchchemical agents may be either toxic chemicals (where inactivation ofneurons is called for), or therapeutic drugs (where therapy isindicated).

A medical procedure performed on a patient's brain, according to theinvention, will now be described in general terms. Followingvisualization of the target tissue by various imaging procedures wellknown in the art, a dual purpose electrode assembly 103 bearing at leastone neuron-monitoring electrode 135 is introduced into the patient'sbrain in the vicinity of the target tissue via introducer tube 101, asdescribed herein. The positioning of the various parts of electrodeassembly 103, including electrode support shaft 137, may then befine-tuned as appropriate. Electrode potentials from cells or tissuesmay then be recorded and the physiological status of the cells ortissues is monitored, over a period of up to several days if necessary.Tissue at the site(s) of the monitored neuron(s) may then be treated.Treatment will vary depending on the patient's overall condition, and/oron the recordings of electrical potentials. For example, treatment maybe in the form of reversible or irreversible inactivation of one or morecells or a region of tissue, or by the delivery of one or moretherapeutic drugs.

Various embodiments of electrode assembly 103 of the instant inventionwill now be described, particularly in the context of performingstereotactic pallidotomy. Other applications and uses of the electrodeassembly will be apparent to the skilled artisan, and are hereby statedto be within the scope of the invention, as delineated by the claimsappended hereto.

Stereotactic Pallidotomy

The globus pallidus is a conical subcortical structure within the brainwhich is involved in the control of movement. FIG. 12A shows the grossmorphology, and relative size of the globus pallidus, as well as itsapproximate location and orientation within the brain. During recentyears, stereotactic pallidotomy has become recognized as a valuableprocedure in the treatment of Parkinson's disease (see, for example,Laitinen, L. Y., et al., “Leksell's posteroventral pallidotomy in thetreatment of Parkinson's disease,” J. Neurosurg., 76:53–61, 1992;Iacono, R. P., et al., “The results, indications, and physiology ofposteroventral pallidotomy for patients with Parkinson's disease,”Neurosurgery, 36:1118–1127, 1995; and references cited therein.) Simplystated, the rationale for the success of this treatment is as follows.Parkinson's disease causes dysfunction due to loss of dopaminergicinnervation in a part of the movement control circuit (Putamen andCaudate) distinct from the globus pallidus. However, because of thenature of the circuit, the dysfunction in Parkinson's disease can beameliorated by disruption of the circuit at the point of the globuspallidus (see, for example, Laitinen, L. Y., et al., “Leksell'sposteroventral pallidotomy in the treatment of Parkinson's disease,” J.Neurosurg., 76:53–61, 1992; Iacono, R. P., et al., “The results,indications, and physiology of posteroventral pallidotomy for patientswith Parkinson's disease,” Neurosurgery, 36:1118–1127, 1995; andreferences cited therein.)

FIG. 12C shows the parallel linear trajectories of electrode assembliesaccording to prior art pallidotomy. As shown, stereotactic pallidotomytechniques of the prior art have relied on the sequential insertion offirst a microelectrode to monitor the physiologic response of neuronswithin a defined region of the globus pallidus, and, if the responsecalls for inactivation (lesioning) of neurons in that region, a second,larger, lesion-producing macroelectrode, or a cryogenic device, istargeted to the same site for the purpose of producing a lesion thereat.This process is repeated until a suitable number of sites within theglobus pallidus have been monitored and, if appropriate, the neuron(s)at that site inactivated. A further feature of prior art pallidotomy isthat the trajectories of the electrodes are perpendicular to the longaxis of the globus pallidus (see for example FIG. 12C) Therefore, theprior art pallidotomy process outlined in the Background of theInvention section of this specification requires the surgeon to makeseveral passes through normal brain tissues during the operation, with aconcomitant risk of brain damage.

The instant invention is concerned with an apparatus including anelectrode assembly including an electrode support shaft, in whichelectrode assembly 103 and electrode support shaft 137 are broadlyequivalent to the multicontact prosthesis 200 and longitudinal electrodesupport 226, respectively, of the neural prosthesis described above.Differences between the recited parts of the respective devices will bereadily apparent to the skilled artisan from their descriptions herein.

Electrode assembly 103 and electrode support shaft 137 of the instantinvention may be either rigid or flexible. In a preferred embodiment,both electrode assembly 103 and electrode support shaft 137 areflexible. In one embodiment electrode support shaft 103 of the instantinvention bears at least one neuron-monitoring electrode 135A/135B. In apreferred embodiment electrode support shaft 103 of the instantinvention bears at least one bipolar neuron-monitoring microelectrode135A. Preferably electrode support shaft 137 includes an outer sheath143 constructed of a flexible polymeric or co-polymeric material. Aparticularly preferred sheath material includes tecoflex-polyurethane(Thermetics, Woburn, Mass.). Preferably electrode support shaft 137bears a plurality of bipolar neuron-monitoring microelectrodes 135A,each bipolar microelectrode 135A including two electrical contacts 136,in the form of a pair of fine wires lying external to, and approximatelyparallel with, the external sheath of the shaft. Each electrical contact136 is coupled to an electrical lead 129 including at least one strandof electrically conductive material, whereby a suitable electric currentmay be conducted to or from each of the electrical contacts 136.Preferably each electrical lead 129 includes a flexible wire coated withan electrically insulating material. More preferably each strand ofelectrically conductive material includes platinum and iridium, and hasa diameter in the range of 10–200 micrometers, more preferably in therange of 20–100 micrometers and most preferably in the range of 30–70micrometers. In a preferred embodiment the electrically insulatingmaterial coating each electrical lead includes polytetrafluoroethene(Teflon®). In another embodiment electrode support shaft 137 ofelectrode assembly 103 is flexible, bears a plurality of bipolarneuron-monitoring microelectrodes 135A, and is equipped with a magnetictip 133 at its distal end. Magnetic tip 133 of the electrode supportshaft 137 is responsive to an external magnetic field, thereby allowingfor its maneuverability in response to controlled changes in an appliedmagnetic field. The magnetic manipulation of medical devices within apatient's body, in general, including magnetic stereotactic procedures,is known in the art (see, for example Grady, M. S., et al. “Magneticstereotaxis: a technique to deliver stereotaxic hypothermia,”Neurosurg., 27:1010–1016, 1990; Grady, M. S., et al., “Nonlinearmagnetic stereotaxis: Three dimensional, in vivo remote magneticmanipulation of a small object in canine brain,” Med. Phys., 17:405–415,1990; Gillies, G. T., et al., “Magnetic manipulation instrumentation formedical physics research,” Rev. Sci. Instrum., 65:533–562, 1994, andreferences cited therein.

In one embodiment of the invention, each bipolar microelectrode 135A isin the form of a pair of fine wires closely juxtaposed on electrodesupport shaft 137, and is capable of monitoring the activity of anindividual neuron or cell by outputting electrical signals indicative ofthe physiological status of the particular neuron or cell. Thephysiological status of a neuron or cell may be used to determinewhether to inactivate the particular neuron or cell.

Under the invention, neurons targeted for inactivation may beinactivated by a variety of different mechanisms and for various timeperiods. For example, neurons may be inactivated by exposure toradiation, infusion of a toxic chemical, cryogenic treatment (cooling),or prolonged electrical stimulation. A toxic chemical, under theinvention, may be a chemical known to be a neurotoxin or a broadspectrum cytotoxin. Cryogenic treatment may be administered from atleast one miniaturized cryogenic device located at one or more specificsites on the electrode support shaft. A preferred mechanism forinactivating neurons is by exposure to radio frequency (RF) radiation,using, for example, a RF lesion generator system such as model RFG-3Cmanufactured by Radionics (Burlington, Mass.). These examples should notbe considered to limit the invention as defined by the claims in anyway.

Inactivation of neurons may be reversible or irreversible. In general,inactivation of neurons resulting from cooling or electrical stimulationis, to some extent, reversible; whereas neuron inactivation by exposureto radiation or infiltration of a toxic chemical normally results in apermanent lesion and is irreversible.

In a preferred embodiment, electrode support shaft 137 is flexible, isequipped with a magnetic tip 133 responsive to an applied externalmagnetic field, and bears a plurality of neuron-monitoringmicroelectrodes 135A and a plurality of neuron-inactivating sitespositioned along electrode support shaft 137. In a more preferredembodiment, electrode support shaft 137 is flexible, is equipped with amagnetic tip 133 responsive to an applied external magnetic field, andbears a plurality of bipolar neuron-monitoring microelectrodes 135A andan equal number of neuron-inactivating sites positioned along electrodesupport shaft 137, wherein each of the plurality of bipolarneuron-monitoring microelectrodes 135A is positioned, along thelongitudinal axis of electrode support shaft 137, coincidental with oneof the neuron-inactivating sites. Each neuron-inactivating site iscapable of inactivating one or more neurons located adjacent to thatsite. A plurality of bipolar neuron-monitoring microelectrodes 135A maybe located at different points on the circumference of electrode supportshaft 137, in other words, the position of the microelectrodes may beoffset with respect to the long axis of the electrode support shaft. Inanother embodiment of the dual purpose electrode support shaft 137, aplurality of bipolar neuron-monitoring microelectrodes 135A may belocated at different points on the circumference of electrode supportshaft 137 but at the same longitudinal position on the support shaft.For example, two bipolar neuron-monitoring microelectrodes 135A may bediametrically opposed, as shown in FIG. 11B. This latter arrangementallows for the simultaneous recording of two action potentials, one fromeach side of the support shaft. In one embodiment of the invention, eachneuron-inactivating site on electrode support shaft 137 is in the formof a delivery port 141 for releasing a lesion-producing toxic chemical.Each delivery port 141 may be activated to release a measured dose of atoxin to the neuron(s), cell(s), or tissue targeted for inactivation,thereby inducing a localized lesion thereat. Many cytotoxic chemicalsare known in the art, and may be used either alone (unconjugated), orconjugated to a specific monoclonal antibody or other carrier molecule(see, for example Stan, A. C., et al., “In vivo inhibition ofangiogenesis and growth of the human U-87 malignant glial tumor bytreatment with an antibody against basic fibroblastic growth factor,” J.Neurosurg., 82:1044–1052, 1995.) One example of a cytotoxic chemical isibotenic acid which selectively destroys cell bodies without damagingfibers of passage (Guldin, W. O. & Markowitsch, H. J., “No detectableremote lesions following intrastriatal injections of ibotenic acid,”Brain Res., 225:446–451, 1992.

In another embodiment of the invention, each neuron-inactivating site onelectrode support shaft 137 is in the form of a macroscopic stimulatingelectrode capable of chronic electrical stimulation of the neuron(s),cell(s), or tissue targeted for inactivation, thereby inducinglocalized, transient neuron dysfunction. With this type of treatmentneuron function is generally regained some time after cessation ofelectrical stimulation.

In a further embodiment of the invention, each neuron-inactivating siteon electrode support shaft 137 is in the form of a cryogenic device,i.e. an element which causes localized cooling of those neurons ortissues with which it is in physical contact. Generally, neuroninactivation resulting from cooling is reversible, and neuron functionis restored after a period of time following cessation of treatment.

In another embodiment of the invention, each neuron-inactivating site onelectrode support shaft 137 is in the form of a lesion-producingmacroelectrode 139, which when energized delivers radio frequency (RF)energy to the neuron(s), cell(s), or tissue targeted for inactivation,thereby inducing a localized lesion thereat.

Although neuron inactivation is described herein primarily withreference to lesion production via macroelectrodes 139, this should notbe considered as limiting the scope of the invention in any way.

A flexible embodiment of electrode assembly 103 can be initiallyintroduced into the vicinity of the target tissue, such as the globuspallidus, via introducer tube 101 that has previously beenstereotactically inserted into the patient's brain. Introducer tube 101of the instant magnetic pallidotomy device is equivalent to theintroducer described above in connection with neural prosthesis 200.Once inserted in the patient's brain, the magnetic tip 133 of electrodeassembly 103 may be urged forwards by the application of an externalmagnetic field of suitable magnitude and direction. By changing themagnitude and direction of the magnetic field electrode support shaft137 can be directed forwards to varying extent and in differentdirections so that it occupies the desired conformation within thetarget tissue. In this situation, electrode support shaft 137 can be theto be “draped” within the target tissue. Preferably the magnetic fieldis generated by an electromagnet or multi-coil electromagnet systempositioned adjacent to, or surrounding, the head or other appropriatebody part of the patient. The electromagnet or multi-coil electromagnetsystem may be attached to a robotic arm. One or more computers may beused to control movement of the robotic arm, and the magnitude anddirection of the magnetic field, as well as to visualize the locationand movement of the magnetic device within the patient.

The manipulation of magnetic medical devices within the body by theapplication of a magnetic field is described more fully in U.S. Pat. No.4,869,247 and U.S. Pat. No. 5,125,888 both of which are incorporated byreference herein in their entirety. Reference is also made to thefollowing publications: Howard III, M. A., et al., “Magnetic movement ofa brain thermoreceptor,” Neurosurgery, 24: 444–448, 1989; Grady, M. S.,et al. “Magnetic stereotaxis: a technique to deliver stereotaxichypothermia,” Neurosurg., 27:1010–1016, 1990; Grady, M. S., et al.,“Nonlinear magnetic stereotaxis: Three dimensional, in vivo remotemagnetic manipulation of a small object in canine brain,” Med. Phys.,17:405415, 1990; Gillies, G. T.; et al., “Magnetic manipulationinstrumentation for medical physics research,” Rev. Sci. Instrum., 65:533–562, 1994; and references cited therein.

Once the neurons adjacent to neuron-monitoring electrodes 135A/135B andmacroelectrodes 139 have been monitored and subsequently inactivated, ifappropriate, electrode assembly 103 may be withdrawn to a home positionwithin introducer tube 101 by exerting a pulling force on tether line127. Electrode support shaft 137 may then be reintroduced into thepatient and repositioned within the patient's tissues, for example, tosample additional regions within the globus pallidus. As electrodeassembly 103 is reintroduced into the patient, tether line 127 retractsbut its proximal end is retained within the end piece 113 of introducertube 101 by anchor plate 125 which is fixedly attached to the proximalend of tether line 127.

Referring now to the drawings, in which like reference numeralsdesignate like or corresponding elements throughout, there is shown inFIGS. 9–11, 13–17, 20 and 23 various elements, components or embodimentsof an apparatus for introducing the distal end of at least one electrodeassembly 103 into the tissues of a patient. FIGS. 9A, 9B and 9Cillustrate three different embodiments of an electrode support shaft, inwhich support shaft 137 may be rigid (as depicted in FIGS. 9A and 9B) orflexible (as shown in FIG. 9C). Preferably support shaft 137 bears arleast one bipolar neuron-monitoring microelectrode 135A and at least onemacroelectrode 139. Support shaft 137 may have additionally magnetic tip133 as shown in FIG. 9C.

FIG. 10 shows an electrode support shaft 137 having a magnetic tip 133and bearing a plurality of bipolar neuron-monitoring microelectrodes135A. Positioned adjacent to each neuron monitoring microelectrode 135Ais a neuron-inactivating site.

FIGS. 11A and 11B show details of parts of an embodiment of an electrodesupport shaft 137 of a dual purpose electrode assembly 103, bearingbipolar neuron-monitoring microelectrodes 135A, in which the pair ofelectrical contacts 136 of microelectrodes 135A are closely juxtaposed,and are positioned coincidental with, and external to, macroelectrode139.

FIGS. 13A–13C show apparatus for performing magnetic stereotacticsurgery. FIG. 13A shows introducer tube 101 positioned within thepatient's skull. Electrode assembly 103 is passed through introducertube 103 towards the targeted tissue. FIG. 13B shows the electrodeassembly 103 ex situ. Electrode assembly 103 includes tether line 127,anchor plate 125, electrical leads 129 gathered at rubber exit cuff 131,and at its distal end, electrode support shaft 137. FIG. 13C showselectrode assembly 103 housed within introducer tube 101 with sealingcap 119 unattached.

FIG. 14 shows a general cross sectional view of introducer tube 101.Introducer tube 101, may be flexible or rigid in its construction, andincludes elongate cylindrical portion 105 with an open distal end 107,conical neck portion 109 which is continuous with portion 105, and atthe proximal end 111 of introducer tube 101 is located a shortcylindrical end piece 113 continuous with neck portion 109.

In a preferred embodiment the inner wall 115 of introducer tube 101 maybe coated with a physiologically acceptable fluid, prior to theintroduction of electrode assembly 103, in order to serve as a lubricantand to reduce drag on electrode assembly 103 as it travels withinintroducer tube 101.

FIG. 15 shows a more detailed view of the proximal end of introducertube 101 showing electrode assembly 103 positioned substantially withinintroducer tube 101, and with sealing cap 119 (not shown) unattached.From this position, electrode support shaft 137 may be moved fromintroducer tube 101 to target tissues and returned to introducer tube101.

FIG. 16 shows a more detailed view of the proximal end or neck portion109 of introducer tube 101 with sealing cap 119 attached, in which theinner wall 115 of end piece 113 has a seat 117 to accommodate sealingcap 119. Docking platform 121 is rigidly attached to the inner wall 115of introducer tube 101. Docking platform 121 includes a perpendicularretaining wall 123 located at the perimeter of platform 121. Anchorplate 125 attached to tether line 127 is retained on docking platform121 before and during insertion of electrode support shaft 137 into thetarget tissue. However, to return electrode assembly 103 from thepatient to introducer tube 101, anchor plate 125 may be grasped withforceps via the handle 126 of anchor plate 125, and an upward force maythen be applied to tether line 127.

Docking platform 121 may be located at different positions along thelongitudinal axis of introducer tube 101 within the neck portion 109,provided that the handle 126 of anchor plate 125 is accessible to thesurgeon and there is provided sufficient clearance for sealing cap 119to be seated in the fully closed position.

Electrical leads 129, having rubber exit cuff 131, exit introducer tube101 in the region of end piece 113 approximately diametrically oppositethe location of docking platform 121.

FIG. 17 depicts a part of the distal end of an electrode assembly 103according to a preferred embodiment of the invention, in which electrodesupport shaft 137 is positioned within the globus pallidus. Electrodeassembly 103 has a magnetic tip 133 located at the distal end ofelectrode support shaft 137, and a plurality of bipolarneuron-monitoring microelectrodes 135A positioned along the long axis ofelectrode support shaft 137. Each bipolar neuron-monitoringmicroelectrode 135A is capable of monitoring the physiologic activity ofan individual neuron by sensing electrical signals and outputting thesensed signals to a suitable recording means. Preferably, each bipolarneuron-monitoring microelectrode 135A is constructed of a pair ofclosely juxtaposed electrical contacts 136. Each electrical contactincludes a fine wire having a diameter in the range of 5 to 200micrometers, more preferably in the range of 5 to 100 micrometers, andmost preferably in the range of 10 to 40 micrometers. Adjacent to eachbipolar neuron-monitoring microelectrode 135A is located acorresponding, spatially paired, lesion-producing macroelectrode 139.Preferably, the fine wires including electrical contacts 136 of bipolarmicroelelectrodes 135A are sufficiently flexible to “flow” with eachpulsation of the brain tissue, and thereby avoid disturbances in thesurrounding tissues. In contrast, monopolar neuron-monitoringmicroelectrodes of the prior art are shorter and stiffer than those ofthe instant invention, which result in disruption of surrounding tissuesand consequently must be removed within a relatively short period oftime. The flexible, non-disrupting nature of bipolar microelectrodes135A as described herein allows them to remain in situ for an extendedperiod of time, thereby enabling the accumulation of more meaningfulinformation on the physiological status of the particular neurons beingmonitored. Such information is critical in defining exactly where neuroninactivation should be performed; this, in turn, leads to maximumefficacy in the treatment and minimum complications for the patient.

According to a preferred embodiment of the invention, a magneticallytipped dual purpose multicontact electrode assembly 103 is inserted intointroducer tube 101, and electrode assembly 103 is anchored to the innerwall 115 of introducer tube 101 via tether line 127 and anchor plate125. The outside diameter of the electrode support shaft 137, includingmagnetic tip 133, is in the range of 1 to 4 mm, which is in the range ofcurrently used standard stereotaxic biopsy tools. There is sufficientexcess length or slack in electrode assembly 103 and in the attachedelectrical leads 129 and tether line 127 so that the electrode-bearingregion of electrode assembly 103 can be pulled out of introducer tube101 into the target tissue by a suitably applied external magneticfield. Under computer control, the magnetic tip 133 of electrodeassembly 103 is driven into the target tissue along a preselectedtrajectory.

FIG. 18 depicts the movement of a magnetically tipped electrode assembly103 in the direction away from introducer tube 101 towards the apex ofthe globus pallidus. The magnetic tip 133 is directed along the selectedtrajectory by appropriate changes in the magnitude and direction of anapplied external magnetic field.

FIG. 19 shows steps in performing magnetic pallidotomy using a dualpurpose multicontact electrode assembly 103, in which introducer tube101 is first inserted into the patient's skull in step a), electrodeassembly 103 is introduced into introducer tube 101 in step b),electrode assembly 103 is located in the “home” position withinintroducer tube 101 in step c), electrode support shaft 137 of electrodeassembly 103 is directed into the globus pallidus by magnetic movementin step d), sealing cap 119 is placed on end piece 113 of introducertube 101 in step e), electrode support shaft 137 of electrode assembly103 is returned to the “home” position within introducer tube 101 instep f), and electrode assembly 103 is removed from the patient in stepg). In the case of the globus pallidus, the preferred trajectory formovement of electrode support shaft 137 generally runs along its entirelongitudinal axis, and movement of the magnetic tip 133 to the end ofthe selected trajectory should take about 20 minutes. Sealing cap 119can then be attached to the end piece 113 of introducer tube 101,thereby sealing introducer tube 101 at its proximal end 111.

The patient may now be removed from the magnetic surgery suite andreturned to the hospital ward. A number of globus pallidus neurons maynow be monitored for their physiologic activity, and the activitymonitored by each microelectrode 135 may be recorded using a suitablerecording device. Based on the neuronal activity monitored and onphysiologic criteria, a decision can be made whether to inactivate theparticular neuron(s) under study.

If inactivation of a particular neuron is called for, a lesion may bemade by energizing the appropriate lesion-producing macroelectrode(s)139 with a suitable electric current. Preferably, the energy used toproduce lesions is in the radio frequency (RF) range. The functionalconsequences of neuron inactivation can then be assessed by testing thepatient on the hospital ward. If the results are satisfactory, theelectrode assembly 103 may be removed. Alternatively, it may bedesirable to monitor other neurons which are located at differentregions within the globus pallidus. In the latter case sealing cap 119is first removed from introducer tube 101.

As depicted in FIG. 20, the handle 126 of anchor plate 125 may begrasped with forceps and an upward force exerted on tether line 127,whereby electrode assembly 103 is “reloaded”or returned to the homeposition within introducer tube 101. The magnetic tip 133 of electrodeassembly 103 may now be redirected, again by the application of asuitable external magnetic field, along a second preselected trajectoryuntil it once again occupies the desired conformation within the targettissue. The process of monitoring and selectively inactivatingindividual neurons may then be repeated. A method for performingpallidotomy according to one embodiment of the instant invention isillustrated by way of Example 1.

FIG. 21 shows steps in making a dual purpose multicontact electrodeassembly useful in performing magnetic stereotactic surgery, whereinthere is provided in step a) an electrode support shaft 137 bearingelectrical leads 129 for coupling to bipolar microelectrodes 135A andmacroelectrodes 139, a plurality of bipolar microelectrodes 135A areattached to electrode support shaft 137 in step b), each of a pluralityof macroelectrodes 139 is attached to electrode support shaft 137adjacent to each of the plurality of bipolar microelectrodes 135A instep c), a magnetic tip 133 is affixed to electrode support shaft 137 instep d), tether line 127 and anchor plate 125 are attached to electrodesupport shaft 137 at a position on 137 remote from the bipolarmicroelectrodes 135A and the macroelectrodes 139 in step e), and rubberexit cuff 131 encompasses electrical leads 129 in step f).

FIG. 22 shows steps in making introducer tube 101, wherein there isprovided an elongate cylinder 105 in step (i), first narrower end ofconical neck portion 109 is rigidly attached coaxially to elongatecylinder 105 in step (ii), cylindrical end piece 113 is rigidly attachedcoaxially to second broader end of conical neck portion 109 in step(iii), docking platform 121 including retaining wall 123 is rigidlyattached to the inner wall of cylindrical end piece 113 in step (iv),and sealing cap 119 is provided in step (v).

Targeted Delivery of Therapeutic Drugs

One embodiment of a dual purpose stereotactic electrode assembly 103,under the invention, may be used to deliver a measured dose of one ormore therapeutic drugs to specific regions of tissues or organsundergoing treatment. In this regard, one or more cells within suchregions of tissues, or such regions of tissue themselves, may have beenpreviously monitored for their physiological activity, by means of atleast one monitoring electrode 135 mounted on electrode support shaft137 of electrode assembly 103, prior to drug delivery. Thus, monitoringelectrodes 135 on electrode support shaft 137 may be multipolarmicroelectrodes 135A which are capable of monitoring action potentialsfrom individual cells, or they may be monopolar electrodes 135B capableof recording field potentials from a region of tissue.

The dual purpose cell monitoring/drug delivering electrode assemblyembodiment of the invention is particularly useful for delivering ameasured dose of a therapeutic drug to a region of previously-monitoredtissue within the human brain. Such an electrode assembly 103 may beused, for example, in the treatment of epilepsy by the release of atherapeutic drug to specific regions of the cerebral cortex followingmonitoring of those regions with monitoring electrodes.

Referring now to FIG. 23, there is provided a dual purpose electrodesupport shaft 137 of an electrode assembly 103, bearing a plurality ofmonitoring electrodes 135 and a plurality of delivery ports 141, whichis capable of both monitoring the physiological activity of individualcells or tissues, and delivering a therapeutic drug to a specific sitewithin a patient's tissues. Such an electrode support shaft, and theelectrode assembly as a whole, is particularly suited to delivering atherapeutic drug to a specific site within a patient's brain. In oneembodiment, such a dual purpose electrode support shaft 137 bears atleast one bipolar neuron-monitoring microelectrode 135A capable ofmonitoring action potentials from individual neurons, and has at leastone delivery port 141 capable of releasing a therapeutic drug. Inanother embodiment, a dual purpose electrode support shaft 137 bears atleast one monopolar neuron-monitoring electrode 135B capable ofmonitoring field potentials from regions of brain tissue, and has atleast one delivery port 141 capable of releasing a therapeutic drug. Inyet another embodiment, a dual purpose electrode support shaft 137 bearsat least one bipolar neuron-monitoring microelectrode 135A capable ofmonitoring action potentials from individual neurons, and further bearsat least one monopolar electrode 135B capable of monitoring fieldpotentials from regions of brain tissue, and has at least one deliveryport 141 capable of releasing a therapeutic drug.

The drug-delivering embodiments of the electrode support shaft 137 maybe used, under the invention, as an integral part of a flexible,multicontact, dual purpose, magnetically tipped electrode assembly 103,substantially as described above in the context of stereotacticpallidotomy, and may be similarly used in conjunction with introducertube 101, also described above. The procedures of introducing andpositioning electrode support shaft 137 within the target tissue may beperformed substantially as described above in the context of magneticstereotactic surgery, under the invention, and/or according to prior artstereotactic medical procedures.

The method of infusing drugs through small openings in the braincatheter would be similar to that described by Lieberman, et al.(Lieberman, et al., “Convection-enhanced distribution of large moleculesin gray matter during interstitial drug infusion,” J. Neurosurg.,82:1021–1029, 1995.)

Delivery ports 141 may be positioned along support shaft 137 in adefined spatial relationship with neuron-monitoring electrodes 135A/135Bto permit accurate delivery of the drug to the target tissue.

Each drug delivery port 141 may be coupled to at least one drug deliverysupply line 145, and each supply line may be connected, through a valveto a suitable mechanism for delivering a liquid. For example, surgicaltubing, valves, and pumps known in the art may be used, or adapted foruse, in conjunction with the apparatus of the instant invention. Asuitable liquid delivering mechanism may in turn be connected to avariable volume reservoir for storing a suitable dose of a therapeuticdrug to be delivered during treatment of the target tissue. Drugdelivery may then be enacted by the simple expedient of opening thevalve and activating a pump, until the reservoir is emptied, or until asuitable measured dose has been released. Each variable volume reservoirand pumping means may be linked to a single delivery port 141, or to aplurality of delivery ports 141. In the latter case, by selectivelyactivating the valve which controls fluid flow to each delivery port141, the exact site(s) of drug delivery can be controlled.

Referring now to FIG. 25, there is shown one embodiment of a dualpurpose neuron-monitoring/drug delivery electrode support shaft, bearinga plurality of multipolar neuron-monitoring microelectrodes 135A, and anequal number of spatially paired drug delivery ports 141. Each drugdelivery port 141 is connected via a drug delivery supply line 145 to areservoir/pump unit 147 for storing and dispensing a drug. The pluralityof drug delivery supply lines 145 are distributed to their respectiveplurality of reservoir/pump units 147 by way of a drug delivery supplyline manifold cap 148 located towards the proximal end of electrodeassembly 103. The location of a plurality of drug delivery supply lines145 within the hollow body of the electrode support shaft 137 is shownin FIGS. 26A, 26B.

The dual purpose neuron monitoring/drug delivery electrode assembly 103described above may be used to administer therapeutic drugs to patientssuffering from various disorders of the brain, including both chronic(e.g. epilepsy) and acute (e.g. cerebral aneurysm) conditions. Forexample, in the case of medically refractory epilepsy, the dual purposeneuron-monitoring/drug delivery electrode assembly 103 including aflexible magnetically tipped electrode support shaft 137 may be insertedthrough a burr hole in the patient's skull via introducer tube 101, suchthat the magnetic tip 133 of support shaft 137 is approximately in adesired location within the patient's skull. In the magnetic surgerysuite, electrode support shaft 137 may be magnetically manipulated undercomputer control until it occupies the desired position. The location ofneuron-monitoring electrodes 135A/135B may be documented in apost-implantation imaging study. Once electrode support shaft 137 issuitably positioned, acute intraoperative monitoring of neurons incontact with electrodes 135A/135B may be undertaken. Alternatively, thepatient may be taken from the magnetic surgery suite to the epilepsymonitoring unit, and the physiological activity of a number of neuronsmay then be monitored chronically, using multipolar microelectrodes135A, over a period of a number of days. All data generated during thistime can be stored using a multichannel tape recorder (Racal, Herndon,Va.), and may be analyzed off-line in the laboratory. Based on the datathus obtained and on criteria of physiologically normal parameters, aninformed decision can be made as to whether drug treatment is indicated,and if so, the optimum treatment regime (nature of the drug, dosage,etc.) to be followed. Subsequently an appropriate dose of one or moretherapeutic drugs may be selectively released from one or more drugdelivery ports 141 positioned on electrode support shaft 137.

The functional consequences of drug treatment may be assessed either inthe epilepsy monitoring unit prior to removal of the dual purposeelectrode assembly 103, or subsequently. If, after assessing thepatient, further treatment is indicated, either an additional dose ofthe same drug, or a first dose of a different drug, may be administeredto those neurons that have already been monitored. Further, if patientassessment in the epilepsy monitoring unit indicates that it isdesirable to monitor, and potentially administer a therapeutic drug to,additional neurons located at a different site of the cerebral cortex,electrode assembly 103 may be retracted into introducer tube 101, andthe patient returned to the magnetic surgery suite. The above processmay be repeated until a satisfactory result is achieved. A method fortargeted delivery of therapeutic drugs to a patient, according to oneembodiment of the invention, is described in Example 2.

As will be readily apparent to the skilled artisan, epilepsy treatmentmay also be performed by the selective inactivation of previouslymonitored neurons or regions of brain tissue, substantially according tothe methods and apparatus, under the invention, described herein in thecontext of stereotactic pallidotomy. As discussed above, neuroninactivation may be effected by various treatments, includingirradiation, treatment with a toxic chemical, cryogenic treatment andchronic electrical stimulation.

Hypothalamic Obesity Probe

There now follows a description of a hypothalamic obesity probeapparatus according to one embodiment of the invention, as well asmethods of using the same.

FIG. 27A shows a perspective view of a hypothalamic stimulation trialselectrode assembly or hypothalamic obesity probe (HOP) 1101 according toone embodiment of the invention. HOP 1101 is for stereotactic placementin the hypothalamus of an obesity patient, and includes a macrocatheter1103 which may house at least one electrode support shaft 1105. Eachelectrode support shaft 1105 may be fine caliber to very fine caliber.

Each of the at least one electrode support shafts 1105 bears a pluralityof electrical contacts 1107 arranged longitudinally on each electrodesupport shaft 1105. Preferably each of the plurality of electricalcontacts 1107 is arranged on each electrode support shaft 1105 in such amanner that plurality of electrical contacts 1107 do not protrude fromelectrode support shaft 1105. Each of the plurality of electricalcontacts 1107 may have its own electrical lead, and can be independentlycontrolled. Each of the plurality of electrical contacts 1107 iselectrically coupled to an electrical stimulation device (not shown).The electrical stimulation device allows for transmission of electricalsignals to each of the plurality of electrical contacts 1107. Further,each of the plurality of electrical contacts 1107 may be capable ofindependently outputting electrical discharges to the hypothalamus. TheFOP may be programmed to determine: which of the plurality of electricalcontacts 1107 output electrical discharges, when electrical dischargesare output from the plurality of electrical contacts 1107, and also thefrequency of the electrical discharges outputted from the plurality ofelectrical contacts 1107.

Each electrical contact 1107 may function as a monopolar stimulationelectrode; or according to another embodiment, each pair of electricalcontacts 1107 may function as a bipolar stimulation electrode. By“stimulation electrode” is meant one or more electrical contacts whichis/are capable of transmitting or delivering electrical discharges, tonearby neurons, at either a relatively low frequency or a relativelyhigh frequency, wherein the electrical discharges may cause eitherexcitation (activation) or inhibition of the nearby neurons.Analogously, by “stimulating” neurons is meant a process or step fordelivering one or more electrical discharges from one or more electricalcontacts to one or more nearby neurons, the one or more electricaldischarges at either a relatively low frequency or a relatively highfrequency, wherein the one or more electrical discharges may causeeither excitation (activation) or inhibition of the nearby neurons.

Electrical discharges of relatively low frequency (e.g. circa 50 Hz) andthose of relatively high frequency (e.g. circa 200 Hz) are expected tohave opposite functional effects on nearby neurons: excitation andinhibition of surrounding tissue, respectively. This is directlyrelevant to the use of the HOP as an electrode assembly for performingstimulation trials on the manipulation of hypothalamic function as ameans for regulating the appetite of an individual, i.e. the HOP is usedto test the effect on appetite control of variable electricalstimulation frequencies in different regions of the hypothalamus. Thus,if an inhibitory electrical discharge (of relatively high frequency) isdelivered to neurons in a portion of the hypothalamus that functions toincrease appetite, a decrease in appetite may result. Similarly, if anexcitatory electrical discharge (of relatively low frequency) isdelivered to neurons in a portion of the hypothalamus that functions todecrease appetite, a decrease in appetite will once again be expected.Consequently, the concept of multi-frequency electrical stimulation ofthe hypothalamus associated with the HOP provides two optionalapproaches to curbing the appetite of an obesity patient, and at thesame time increases the likelihood of finding regions of thehypothalamus which are responsive to appetite control via electricalstimulation. The likelihood of finding regions of the hypothalamus whichare responsive to appetite control via electrical stimulation may befurther increased by the use of a plurality of electrode support shafts1105, as well as by the use of a plurality of electrical contacts 1107arranged longitudinally on each of the electrode support shafts 1105.

Thus, stimulation trials hypothalamic electrode assembly or HOP 1101, asdescribed above, may be introduced via an introducer tube (not shown inFIG. 27A) through a burr hole in the patient's cranium to a locationadjacent the hypothalamus, whence at least one electrode support shaftmay be inserted in the hypothalamus. According to a preferred embodimentof the invention, a plurality of electrode support shafts may beinserted in the hypothalamus. By monitoring the clinical effect ofelectrical discharges of different frequencies and from differentstimulation electrodes located in different selected portions or regionsof the hypothalamus, the neurosurgeon may determine which portions ofthe hypothalamus are likely to provide a clinically useful result (i.e.the long term suppression of appetite of the obesity patient) followingchronic electrical stimulation. The HOP may then be programmed toprovide electrical discharges of suitable frequencies, periodicities,etc. from selected stimulation electrodes, in order to mimic orduplicate the monitored clinical effects on appetite suppression.

Alternatively, according to another embodiment of the invention, bymonitoring the clinical effect of electrical discharges of differentfrequencies and from different stimulation electrodes located indifferent selected portions or regions of the hypothalamus, theneurosurgeon may determine an appropriate region of the hypothalamus inwhich to position a chronic electrical stimulation device (not shown)for the long term suppression of appetite of the obesity patient. Such achronic electrical stimulation device may be pre-programmed prior toinsertion in the hypothalamus to provide electrical discharges ofsuitable frequencies, periodicities, etc. in order to mimic or duplicatethe clinical effects of appetite suppression as observed followingelectrical stimulation using the HOP.

According to a preferred embodiment of HOP 1101, 1101′ (FIG. 27B), eachstimulation electrode or electrical contact 1107 is capable ofindependently outputting electrical discharges in the frequency range offrom about 10 to about 400 Hz, i.e. spanning the entire frequency rangeof electrical discharges from relatively low frequency to relativelyhigh frequency.

Macrocatheter 1103 may house from one electrode support shaft 1105 todozens of electrode support shafts 1105. Preferably macrocatheter 1103may house from two to about 10 electrode support shafts 1105. Eachelectrode support shaft 1105 includes a plurality of stimulationelectrodes or electrical contacts 1107. Preferably, the HOP of theinvention includes a sufficient number of electrode support shafts and asufficient number and arrangement of stimulation electrodes 1107 thatthe entire hypothalamus can be mapped during a single insertion of themacrocatheter into the brain of the patient. By mapping of thehypothalamus is meant monitoring the response of different regions ofthe hypothalamus to electrical discharges from stimulation electrodes.Each stimulation electrode 1107 may be coupled to a single electricalsimulation device (not shown) by electrical leads 1106.

FIG. 27B shows a HOP or stimulation trials electrode assembly 1101′,according to another embodiment of the invention, in which macrocatheter1103 may include a magnetic unit 1104 secured thereto to permit magneticstereotactic placement of macrocatheter 1103 at a predetermined locationwithin the patient's brain. Preferably, the predetermined location forplacement of macrocatheter 1103 within the patient's brain is adjacentto the hypothalamus. In a preferred embodiment, magnetic unit 1104 issecured at the distal end of macrocatheter 1103. In one embodiment,magnetic unit 1104 is in the form of a magnetic collar secured at thedistal end of macrocatheter 1103.

FIG. 28A shows a cross-sectional view of the distal end of a singleelectrode support shaft 1105 of HOP 1101, according to one embodiment ofthe invention, in which two electrical contacts 1107 are each separatelycoupled via electrical leads to an electrical stimulation device (notshown), and each electrical contact 1107 functions separately as amonopolar stimulation electrode.

FIG. 28B shows a cross-sectional view of the distal end of a singleelectrode support shaft 1105 of HOP 1101 with two bipolar electrodes,including a total of four electrical contacts 1107 each separatelycoupled via electrical leads to an electrical stimulation device (notshown), according to another embodiments of the invention.

Hypothalamic Drug Microinfusion Assembly

There now follows a description of a hypothalamic drug microinfusionassembly according to another embodiment of the invention, as well asmethods of using the same.

FIG. 29A shows a perspective view of a hypothalamic drug infusionassembly 1001, according to another embodiment of the invention. Druginfusion assembly 1001 includes a macrocatheter 1003 which may house atleast one microinfusion catheter 1005 for placement in the hypothalamus.Each microinfusion catheter 1005 may be fined calibrated to very finecalibrated diameter.

Each of the at least one microinfusion catheters 1005 is functionallycoupled to a drug delivery manifold 1009. A drug supply line 1011 isfunctionally coupled to drug delivery manifold 1009, and a drugreservoir/pump 1013 for retaining and pumping a drug is functionallycoupled to drug supply line 1011. Each of the at least one microinfusioncatheters 1005 may have a plurality of drug delivery ports 1007 (FIG.30).

While in use, drug reservoir/pump 1013 is located subcutaneously andadjacent to the cranium. Drug reservoir/pump 1013 pumps a drug at avariable rate, and the variable rate of pumping a drug may be controlledpercutaneously by a radio control unit (not shown), the latter wellknown in the art. Drug reservoir/pump 1013 may include a valve 1015,such as a recharge valve for recharging reservoir/pump 1013 with aquantity of a drug. The term “drug” as used herein means any chemicalentity, whether natural, synthetic, or semisynthetic, or derivativesthereof, which exhibit a pharmacological effect related to appetiteregulation, and may include various neurotransmitters and regulatorymolecules. According to a preferred embodiment of the invention, valve1015 may be accessible externally or percutaneously.

FIG. 29B shows a perspective view of a hypothalamic drug infusionassembly 1001′, according to another embodiment of the invention. Druginfusion assembly 1001′ is similar to drug infusion assembly 1001, withthe exception that the former includes a magnetic unit 1004. Accordingto a currently preferred embodiment, magnetic unit 1004 is located atthe tip or distal end of macrocatheter 1003 as a collar secured to theperimeter of macrocatheter 1003. Magnetic unit allows for the magneticstereotactic placement of macrocatheter 1003 at a specific locationwithin the brain, for example placement at a location adjacent to thehypothalamus.

FIG. 30 shows a perspective view of the distal end of macrocatheter 1003of hypothalamic drug infusion assembly 1001, showing three microinfusioncatheters 1005 protruding therefrom, according to one embodiment of theinvention. It is to be understood that, whereas three microinfusioncatheters 1005 are depicted in FIG. 30, the actual number ofmicroinfusion catheters 1005 housed within macrocatheter 1003 could begreater or lesser than three, or may equal three. Each microinfusioncatheter 1005 includes a plurality of drug delivery ports 1007. Eachdrug delivery port 1007 may be fine caliber to very fine caliber. Eachof the plurality of drug delivery ports 1007 is independentlycontrollable and capable of independently outputting a drug; and each ofthe plurality of drug delivery ports 1007 is therefore capable ofindependently delivering a drug to a separate site within thehypothalamus of a patient. The amount of drug outputted from theplurality of drug delivery ports 1007 is determined by reservoir/pump1013, the latter capable of pumping a drug at a variable pumping ratewhich may be controlled percutaneously by radio control as discussedhereinabove.

FIG. 31 summarizes steps involved in a method for treating an obesitypatient by outputting electrical discharges from a HOP to selectedportions of the patient's hypothalamus, according to a currentlypreferred embodiment of the invention. Thus, step 901 involves obtaininga three dimensional (digital) image of a patient's brain, the imageincluding, and showing the position or location of the hypothalamus.Step 903 involves inserting a macrocatheter of a HOP (e.g. 1101′, FIG.27B) adjacent to the hypothalamus. The macrocatheter may be introducedvia an introducer tube (not shown) through a burr hole formed in thepatient's cranium. At least one electrode support shaft is inserted intothe hypothalamus in step 905, wherein the at least one electrode supportshaft bears a plurality of longitudinally arranged stimulationelectrodes. Preferably step 905 involves inserting a plurality ofelectrode support shafts within the hypothalamus, each of the pluralityof electrode support shafts bearing a plurality of longitudinallyarranged stimulation electrodes, and each of the plurality ofstimulation electrodes being capable of independent control, whereby amultitude of target areas or portions of the hypothalamus can be sampledfollowing a single surgical procedure. Then, step 907 involvesoutputting electrical discharges from at least one of the plurality ofstimulation electrodes, thereby stimulating at least one neuron in thehypothalamus. Step 909 then involves observing and/or monitoring theclinical effect or clinical effects of step 907. In this way, the entirehypothalamus may be mapped to determine those particular stimulationelectrodes of the plurality of stimulation electrodes which will providea clinically useful result or effect. Step 910 involves deliveringelectrical discharges from those particular stimulation electrodes ofthe plurality of stimulation electrodes determined in step 909 toprovide a clinically useful result. The HOP may be programmed for thechronic output of suitable electrical discharges from those particularstimulation electrodes determined to provide a clinically useful result.

FIG. 32 is a schematic representation of steps involved in a method fortreating an obesity patient, according to another embodiment of theinvention, in which a three dimensional (digital) image of a patient'sbrain is obtained in step 901. Step 903 then involves inserting amacrocatheter of a HOP (e.g. 1101′, FIG. 27B) adjacent to thehypothalamus, wherein the HOP includes a plurality of electrode supportshafts. The plurality of electrode support shafts are inserted into afirst region, or region I, of the hypothalamus in step 905, wherein eachof the plurality of electrode support shafts bear a plurality oflongitudinally arranged stimulation electrodes. Then, step 907 involvesstimulating a plurality of neurons in the first region of thehypothalamus by delivering electrical discharges from the plurality ofstimulation electrodes. Step 909 then involves observing and/ormonitoring the clinical effects of step 907. If a useful clinical effectis not observed in step 909, step 911 involves removing the plurality ofelectrode support shafts from region I of the hypothalamus, andreinserting the plurality of electrode support shafts, bearing aplurality of longitudinally arranged stimulation electrodes, into asecond region, or region II, of the hypothalamus. Step 913 involvesstimulating a plurality of neurons in region II of the hypothalamus bydelivering one or more electrical discharges from the plurality ofstimulation electrodes to neurons in region II. Step 915 involvesobserving and/or monitoring the clinical effects of step 913 todetermine those particular stimulation electrodes of the plurality ofstimulation electrodes which will provide a clinically useful result oreffect. Based on the clinical effects observed in step 915, step 917involves delivering electrical discharges from those particularstimulation electrodes of the plurality of stimulation electrodesdetermined in step 915 to provide a clinically useful result. The HOPmay be programmed for the chronic output of suitable electricaldischarges from those particular stimulation electrodes determined toprovide a clinically useful result.

It is to be understood that, according to the invention, a “region” ofthe hypothalamus may refer to a region or volume of the hypothalamuswhich lies in the vicinity of a single electrode support shaft 1105 andis “targeted” (or sampled) by that single electrode support shaft 1105,or “region” of the hypothalamus may refer to a plurality of regions orvolumes, wherein each of the plurality of regions or volumes is targetedsimultaneously by a plurality of electrode support shafts 1105.

By “region I” or “first region” of the hypothalamus is meant that regionor group of regions targeted as a result of a first insertion of atleast one electrode support shaft 1105 into the hypothalamus. By “regionII” or “second region” of the hypothalamus is meant a second, third, orany additional number of randomly or otherwise selected regions targetedas a result of a corresponding second, third, or any additional numberof insertions of at least one electrode support shaft 1105 into thehypothalamus.

FIG. 33 schematically summarizes steps involved in a method for treatingan obesity patient by microinfusing a drug into one or more selectedportions of the hypothalamus of a patient, according to anotherembodiment of the invention, wherein step 901 involves obtaining animage of the hypothalamus of the patient. Step 921 then involvesinserting a macrocatheter into the patient's brain adjacent to thehypothalamus. The macrocatheter houses at least one microinfusioncatheter. Each microinfusion catheter includes a plurality ofindependently controllable drug delivery ports, each of the plurality ofdrug delivery ports being functionally coupled to a drug supply line.Under the invention, the macrocatheter may be inserted adjacent to thehypothalamus via a burr hole in the patient's cranium, and themacrocatheter may be introduced into the patient's brain via anintroducer tube (not shown) inserted into the burr hole. Step 923involves inserting the at least one microinfusion catheter into thehypothalamus. Thereafter, step 925 involves sequentially infusing a drugfrom various members of the plurality of delivery ports on the at leastone microinfusion catheter into corresponding sites of the hypothalamusproximate the various members of the plurality of delivery ports. Step927 involves observing and/or monitoring the clinical effect of step925, in order to determine which of the various members of the pluralityof delivery ports will provide a useful clinical result. Finally, step928 involves delivering a drug from those selected members of theplurality of delivery ports determined in step 927 to provide a usefulor desired clinical effect.

FIG. 34 is a schematic representation of steps involved in a method fortreating an obesity patient by microinfusing a drug from at least onemicroinfusion catheter into the hypothalamus of the patient, accordingto another embodiment of the invention. Thus, step 901 involvesobtaining an image of the hypothalamus of the patient. Step 921 theninvolves inserting a macrocatheter into the patient's brain adjacent tothe hypothalamus. Step 923 involves inserting at least one microinfusioncatheter into a first region, or region I, of the hypothalamus. Step 925involves sequentially infusing a drug from various members of the atleast one drug delivery port on the at least one microinfusion catheterinto a site within region I of the hypothalamus adjacent to the at leastone drug delivery port. Step 927 involves observing and/or monitoringthe clinical effect of step 925. In the event that a useful clinicaleffect is not observed in step 927, step 929 involves removing the atleast one microinfusion catheter from region I of the hypothalamus andreinserting the at least one microinfusion catheter into a secondregion, or region II, of the hypothalamus. Step 931 involvessequentially infusing a drug from various members of the at least onedrug delivery port on the at least one microinfusion catheter into asite within region II of the hypothalamus adjacent to the at least onedrug delivery port. Step 933 involves observing and/or monitoring theclinical effect of step 931, in order to determine which of the variousmembers of the plurality of delivery ports will provide a usefulclinical result. Finally, step 935 involves delivering a drug toselected portions of the hypothalamus from those selected members of theplurality of delivery ports determined in step 933 to provide a usefulor desired clinical effect.

Based on the clinical effect observed following microinfusion of certaindrugs into specific sites within the hypothalamus a suitable drugtreatment regimen may be instigated to effectively suppress the appetiteof an obesity patient over a prolonged period of time. As a result anextended period of weight loss may be followed by a further extended, orindefinite period, of more or less constant body weight in the normalrange for an individual of the patient's height and bone mass.

FIG. 35A is a schematic representation of steps involved in a method fortreating an obesity patient by electrical stimulation of thehypothalamus of the patient, according to a preferred embodiment of theinvention. In step 1201 a three dimensional digital image of thepatient's brain indicating the precise location of the hypothalamus isprovided. Step 1203 involves forming a burr hole at an appropriatelocation in the patient's cranium. Step 1205 involves inserting anintroducer tube into the burr hole; and step 1207 involves introducing amacrocatheter into the introducer tube. The macrocatheter may have amagnetic unit secured to the distal end of the macrocatheter, and themacrocatheter houses at least one electrode support shaft which includesa longitudinal arrangement of a plurality of stimulation electrodes.Step 1209 involves inserting the macrocatheter in a zone of thepatient's brain adjacent to the hypothalamus. The inserting step 1209may include magnetic stereotactic placement of the macrocatheter in azone of the patient's brain adjacent to the hypothalamus, and themagnetic stereotactic placement of the macrocatheter may be performedunder computer control.

Step 1211 involves inserting the at least one electrode support shaftinto the hypothalamus. Step 1213 involves electrically stimulating atleast one neuron in the hypothalamus, by means of electrical dischargesof various frequencies, the electrical discharges outputted by, ordelivered from, one or more of the plurality of stimulation electrodes.Step 1215 involves monitoring the clinical effect of step 1213 to defineregions of the hypothalamus which will provide a desired clinical resultwhen electrical discharges are outputted thereto. Step 1216 involvesoutputting or delivering electrical discharges to defined regions of thehypothalamus over a period of time commensurate with treatment forobesity. Depending on the patient's condition, the period of time fortreatment may range from several days to several years. The definedregions of the hypothalamus to which electrical discharges are deliveredare determined based on the clinical effects of electrical stimulationas monitored in step 1215.

FIG. 35B is a schematic representation of steps involved in a method fortreating an obesity patient by microinfusing a drug from at least onemicroinfusion catheter into the hypothalamus of the patient, accordingto another embodiment of the invention. Steps 1201 to 1215 of the methodof FIG. 35B are substantially as described above for steps 1201 to 1215of the method of FIG. 35A. The method of FIG. 35B then includes theadditional steps 1225 through 1233 as follows. Step 1225 involvesremoving the at least one electrode support shaft from the hypothalamus.Step 1227 involves removing the first macrocatheter from the zone of thepatient's brain. Step 1229 involves inserting a second macrocatheterinto the zone of the patient's brain whence the first macrocatheter wasremoved. The second macrocatheter inserted into the zone of thepatient's brain includes or houses at least one microinfusion catheter,and the at least one microinfusion catheter has a longitudinalarrangement thereon of a plurality of drug delivery ports. Each of theplurality of drug delivery ports is capable of independently outputtingor delivering a drug to a separate site within a given region of thehypothalamus. Step 1231 involves inserting the at least onemicroinfusion catheter of the second macrocatheter into the appropriateregion of the hypothalamus, the appropriate region defined by observinga satisfactory or desired clinical effect when at least one neuronwithin the appropriate region undergoes electrical stimulation,according to the clinical effect observed in step 1215. Step 1233involves infusing a drug from at least one of the plurality of drugdelivery ports to at least one site within the appropriate region of thehypothalamus.

FIG. 35C is a schematic representation of steps involved in a method fortreating an obesity patient by microinfusing a drug from at least onemicroinfusion catheter into the hypothalamus of the patient, accordingto yet another embodiment of the invention. In step 1201 a threedimensional digital image of the patient's brain indicating the preciselocation of the hypothalamus is provided. Step 1203 involves forming aburr hole at an appropriate location in the patient's cranium. Step 1205involves inserting an introducer tube into the burr hole; and step 1207involves introducing a first macrocatheter into the introducer tube. Thefirst macrocatheter may have a magnetic unit secured to the distal endof the first macrocatheter, and the first macrocatheter houses at leastone electrode support shaft which includes a longitudinal arrangement ofa plurality of stimulation electrodes. Step 1209 involves inserting thefirst macrocatheter in a zone of the patient's brain adjacent to thehypothalamus. The inserting step 1209 may include magnetic stereotacticplacement of the first macrocatheter in a zone of the patient's brainadjacent to the hypothalamus, and the magnetic stereotactic placement ofthe first macrocatheter may be performed under computer control.

Step 1211 involves inserting the at least one electrode support shaftinto a selected first region, or region I, of the hypothalamus. Step1213 involves electrically stimulating at least one neuron in theselected first region of the hypothalamus, by means of electricaldischarges outputted by or delivered from the plurality of stimulationelectrodes. Step 1215 involves monitoring the clinical effect of step1213. Step 1217 involves, first the removal of the at least oneelectrode support shaft from the selected first region of thehypothalamus, and then the reinsertion of the at least one electrodesupport shaft in a selected second region, or region II, of thehypothalamus. Step 1221 involves monitoring the clinical effect of step1219. Step 1223 involves repeating steps 1217 through 1221 asappropriate until a satisfactory or desired clinical effect is obtained,and therefore an appropriate region for stimulation of at least oneneuron within the hypothalamus may be defined. Step 1225 then involvesremoving the at least one electrode support shaft from the hypothalamus.Step 1227 involves removing the first macrocatheter from the zone of thepatient's brain.

Step 1229 of FIG. 35C involves inserting a second macrocatheter into thezone of the patient's brain whence the first macrocatheter was removed.The second macrocatheter inserted into the zone of the patient's brainincludes or houses at least one microinfusion catheter, and the at leastone microinfusion catheter has a longitudinal arrangement thereon of aplurality of drug delivery ports. Each of the plurality of drug deliveryports is capable of independently outputting or delivering a drug to aseparate site within a given region of the hypothalamus. Step 1231involves inserting the at least one microinfusion catheter of the secondmacrocatheter into the appropriate region of the hypothalamus, theappropriate region defined by observing a satisfactory or desiredclinical effect when at least one neuron within the appropriate regionundergoes electrical stimulation, according to steps 1217 through 1223.Step 1233 involves infusing a drug from at least one of the plurality ofdrug delivery port to at least one site within the appropriate region ofthe hypothalamus.

FIG. 36A schematically shows steps involved in a method for treating anobesity patient by chronic electrical stimulation of the hypothalamus ofthe patient by implantation in the hypothalamus of a programmablehypothalamic obesity probe, according to a preferred embodiment of theinvention. Step 1301 involves obtaining a three dimensional digitalimage of a patient's brain showing the location of the hypothalamus.Step 1303 involves inserting a macrocatheter into a zone of thepatient's brain adjacent to the hypothalamus. The macrocatheter housesat least one electrode support shaft, and each of the at least oneelectrode support shafts has a plurality of stimulation electrodes. Inturn, each of the plurality of stimulation electrodes is capable ofindependently outputting electrical discharges of various frequencies,for example at any given frequency over the range of from about 10 Hz toabout 400 Hz. Step 1305 involves inserting the at least one electrodesupport shaft into the hypothalamus of the patient. Step 1307 involvesdelivering electrical discharges of various frequencies from a first setof the plurality of stimulation electrodes to a first set of neuronswithin the hypothalamus. Step 1309 involves delivering electricaldischarges of various frequencies from at least one further set of theplurality of stimulation electrodes to at least one further set ofneurons within the hypothalamus. In this regard, a “set” of stimulationelectrodes may be a single member of the plurality of stimulationelectrodes, located at a defined location on a defined member of the atleast one electrode support shafts, which delivers an electricaldischarge to a singe site within the hypothalamus; or, a “set” ofstimulation electrodes may include more than one member of the pluralityof stimulation electrodes, each located at a defined location on one ormore defined members of the at least one electrode support shafts, fromwhich a plurality of electrical discharges are delivered simultaneouslyto a plurality of sites within the hypothalamus. By analogy, a “set” ofneurons may be a single neuron targeted by an electrical discharge froma single stimulation electrode, or a “set” of neurons may include aplurality of neurons targeted simultaneously by a plurality ofsimultaneously transmitted or outputted electrical discharges from acorresponding plurality of stimulation electrodes. Step 1311 involvesmonitoring the clinical effects of steps 1307 and 1309 on appetiteregulation by the patient, in order to determine the clinical effects ofvarious combinations of electrical discharge frequency/location ofstimulation electrodes. Such clinical effects may be monitored on theward over a period of several hours, and subsequently over a moreextended period of a number of days. Step 1313 involves optimizing theelectrical discharges delivered to the neurons within the hypothalamus,according to steps 1307 and 1309, for optimum appetite regulation by thepatient. As alluded to above, step 1313 may include optimizing both thefrequency of the electrical discharges over an extended frequency rangefrom about 10–400 Hz, and the set of stimulation electrodes from whichthe electrical discharges are outputted. In the latter case, the set ofstimulation electrodes from which the electrical discharges areoutputted correspond, or directly relate to, specific target sites orregions within the hypothalamus. Step 1314 involves programming the HOPfor chronic delivery of selected electrical discharges, of definedfrequency and at specific locations within the hypothalamus, asdetermined in step 1313 to provide optimum appetite regulation.

FIG. 36B schematically shows steps involved in a method for treating anobesity patient by chronic electrical stimulation of the hypothalamus ofthe patient by implantation in the hypothalamus of a pre-programmedchronic electrical stimulator, according to another embodiment of theinvention. Steps 1301 to 1313 of the method of FIG. 36B are common tothe method of FIG. 36A as described above. Step 1315 involvespre-programming a chronic electrical stimulator for optimum clinicaleffectiveness in the patient, based on the results of step 1313. Lastly,step 1317 involves implanting the pre-programmed chronic electricalstimulator in an appropriate location within the hypothalamus of thepatient.

EXAMPLE 1

Method of Performing Magnetic Stereotactic Pallidotomy

Introducer tube 101 is stereotactically inserted through a burr hole inthe patient's skull such that the open distal end 107 of introducer tube101 is positioned close to the lateral globus pallidus. A dual purposemulticontact electrode assembly 103 including a flexible electrodesupport shaft 137 having a magnetic tip 133 is inserted into introducertube 101, such that magnetic tip 133 of support shaft 137 isapproximately in a desired location within the patient's brain. Thepatient is brought to the magnetic surgery suite, and electrode supportshaft 137 of electrode assembly 103 is magnetically pulled into theglobus pallidus, generally along the long axis of the globus pallidus,along a preselected trajectory. Once electrode support shaft 137 issuitably positioned to occupy the desired volume within the globuspallidus, the patient is removed from the magnetic surgery suite andreturned to the hospital ward. While on the ward, the physiologicalactivity of a number of globus pallidus neurons is monitored usingbipolar microelectrodes 135A. Based on the recordings of physiologicalactivity thus obtained and on criteria of physiologically normalparameters, radio frequency lesions are made at the site of thoseneurons targeted for inactivation, by energizing the appropriatemacroelectrode(s) 139 with a lesion-producing electric current. Thefunctional consequences of the newly-formed lesions are assessed on theward by testing the patient prior to removal of electrode assembly 103from the patient. If the results are satisfactory, the electrodeassembly is removed. If it is desirable to monitor, and potentiallylesion, additional neurons located within a different volume of theglobus pallidus, electrode assembly 103 is retracted into introducertube 101. The patient is returned to the magnetic surgery suite, and theprocess is repeated until a satisfactory result is achieved.

EXAMPLE 2

Targeted Drug Delivery from a Dual Purpose Electrode Assembly for theTreatment of Epilepsy

Introducer tube 101 is stereotactically inserted through a burr hole inthe patient's skull such that the open distal end 107 of introducer tube101 is positioned within the cerebral cortex. A dual purposeneuron-monitoring/drug delivery electrode assembly 103 including aflexible electrode support shaft 137 having a magnetic tip 133 isinserted into introducer tube 101, such that the magnetic tip 133 ofsupport shaft 137 is approximately in a desired location within thepatient's skull. The patient is brought to the magnetic surgery suite,and electrode support shaft 137 of electrode assembly 103 ismagnetically manipulated until it occupies the desired position. Onceelectrode support shaft 137 is suitably positioned, the patient isremoved from the magnetic surgery suite and taken to the epilepsymonitoring unit, where the physiological activity of a number of neuronsis monitored. Based on the recordings of physiological activity thusobtained and on criteria of physiologically normal parameters, asuitable dose of one or more therapeutic drugs is released from one ormore selected drug delivery ports 141.

The functional consequences of drug treatment is assessed in theepilepsy monitoring unit by testing the patient prior to removal of dualpurpose electrode assembly 103. If the results are satisfactory,electrode assembly 103 is removed from the patient. If it is desirableto monitor, and potentially administer a therapeutic drug to, one ormore different regions of the cerebral cortex, electrode assembly 103 isretracted into introducer tube 101. The patient is then returned to themagnetic surgery suite, and the process is repeated until a satisfactoryresult is achieved.

As will be apparent to the skilled artisan, the apparatus of the instantinvention is particularly suited to performing surgery on the brain, ingeneral, and may be used effectively for performing other medicalprocedures, including but not limited to, thalamotomy, controlledlesioning to treat epilepsy, and targeted delivery of therapeutic drugs.

EXAMPLE 3

Method for Treating Obesity by Hypothalamic Electro-Stimulation

A burr hole is strategically placed in the patient's cranium for thepurpose of stereotactic placement of a macrocatheter of the hypothalamicobesity probe apparatus in a zone of the patient's brain adjacent to thehypothalamus. An introducer tube is stereotactically inserted throughthe burr hole. The macrocatheter, which includes a magnetic collaraffixed at the distal end of the macrocatheter, is inserted into theintroducer tube. The patient is transferred to the magnetic surgerysuite, and the magnetically equipped macrocatheter is magneticallymanipulated such that it is positioned adjacent to the hypothalamus. (Atthis point the patient may be removed from the magnetic surgery suite).At least one electrode support shaft bearing a plurality of stimulationelectrodes is introduced from the macrocatheter into a first region ofthe hypothalamus. Because the plurality of stimulation electrodes arearranged longitudinally on the at least one electrode support shaft,each of the plurality of stimulation electrodes occupies a distinctposition within the hypothalamus. Each of the plurality of stimulationelectrodes is capable of being independently controlled, i.e. each ofthe plurality of stimulation electrodes is capable of independentlyoutputting electrical discharges over a range of frequencies. Followingimplantation of at least one electrode support shaft into thehypothalamus, the patient is transferred to the ward for electricalstimulation trials. Electrical discharges of relatively high or lowfrequency are delivered independently from selected members of theplurality of stimulation electrodes, and the clinical effects areobserved. The specific contacts or stimulation electrodes from whichelectrical discharges are delivered, and the frequencies of theelectrical discharges, are varied in order to determine whichcombination(s) of stimulation electrodes/electrical discharge frequencyprovide a desired or optimal clinical effect. That is to say, theeffects on appetite suppression of electrical stimulation of neurons ata set of locations within the hypothalamus by electrical discharges ofspecific frequency/frequencies delivered from a corresponding set ofstimulation electrodes are observed and recorded. Such observations aremade initially over a period of a few hours, and subsequently over aperiod of several days, as necessary. If the clinical effects observedare deemed unsatisfactory by the physician, a different combination ofstimulation electrodes/electrical discharge frequency may be used. Thatis to say, specific sets of neurons of the hypothalamus are stimulatedby electrical discharges of different frequency/frequencies and/or byelectrical discharges from different stimulation electrodes of the atleast one electrode support shaft, and the effects on appetitesuppression are again observed and recorded.

Once the clinical effects of hypothalamic electrical stimulation aredeemed satisfactory by the physician, the hypothalamic obesity probe maybe programmed to provide chronic electrical discharges from thosestimulation electrodes and at those frequencies observed to provide asatisfactory clinical effect.

EXAMPLE 4

Method for Treating Obesity by Hypothalamic, Site-Specific DrugMicroinfusion

A magnetically tipped first macrocatheter, which houses at least onemicroinfusion catheter, is inserted into a zone of the patient's brainadjacent to the hypothalamus, generally as described above for EXAMPLE3. At least one microinfusion catheter, bearing a plurality ofindependently controllable drug delivery ports, is introduced into thehypothalamus. The clinical effects of various sequentially-administereddrug delivery regimens are monitored; each regimen including a givendosage of a drug delivered from specific members of the plurality ofdrug delivery ports. The clinical effects of a given drug treatmentregimen may be monitored over a period of hours or days. In this way itis possible to define one or more regions of the hypothalamus that isinvolved in appetite regulation, the one or more regions so definedcorresponding to a set of the plurality of drug delivery ports.

The at least one microinfusion catheter is coupled to a miniaturesurgical drug reservoir/pump via surgical tubing using materials andmethods well known in the art. The reservoir/pump is secured to thepatient's cranium beneath the scalp, and the reservoir/pump is activatedto pump a drug, known to regulate appetite when delivered within thehypothalamus, from a defined set of the plurality of drug deliveryports. The rate at which the reservoir/pump pumps a drug may be adjustedempirically in order to obtain the optimum clinical effect.

The Risk Benefit Ratio

i. Neural Prosthesis Risk/Benefit

The clinical usefulness of an auditory neural prosthetic device dependson several variables, most importantly the risk-benefit ratio for agiven device. An ideal device effectively restores hearing without riskto the patient's overall health. Salient features of two types ofdevices are outlined below.

Since primary auditory cortex 150 is situated in temporal lobe 156,neurosurgeons expose this portion of the brain routinely during a widerange of operations. In the non-dominant temporal lobe, unlike thebrainstem, the auditory region is not surrounded by vital structures. Ifa patient is diagnosed with an infiltrating tumor of the non-dominantauditory cortex, for example, the neurosurgeon can resect this tissuewith very little risk of complication.

Another example is temporal lobe surgery for intractable epilepsy. Mostpatients who undergo this surgery are in good general health but sufferfrom seizures periodically. Usually, chronic epilepsy is not a lifethreatening condition, and many patients have seizures for decadesduring which time they are able to work and raise families.

Since most forms of epilepsy are medically “tolerable,” surgicaltreatment directed at curing epilepsy is only justified when it ishighly effective and carries with it very low risk of morbidity andmortality. A properly selected patient in good general health has lessthan a one percent chance of developing a significant neurologiccomplication following an elective non-dominant temporal lobectomy forintractable epilepsy, and a 70 percent chance of being cured of theirseizures. In that setting, the risk/benefit ratio is strongly in thepatient's favor. An operation designed exclusively to place astimulating neural prosthetic electrode onto non-dominant auditorycortex could be carried out under local anesthesia and take less thantwo hours operating time. This procedure would entail even less medicalrisk than a standard epilepsy resection.

ii. Magnetic Pallidotomy Risk/Benefit

Compared with prior art stereotactic pallidotomy, magnetic pallidotomyaccording to the instant invention has, in theory, less risk and greaterbenefit to the patient, for the following reasons. Because of theability of the electrode support shaft to be directed to occupy aspecific conformation within the target tissue and the presence of aplurality of neuron-monitoring microelectrodes, a target volume of theglobus pallidus can be accesses, and neurons from a number of siteswithin that target volume can be monitored with a single pass throughthe brain. In contrast, neuron-monitoring electrodes of the prior artwould need to be passed through the brain a number of times to access anequivalent volume of target tissue.

Secondly, by combining the functions of neuron-monitoring andlesion-production in a single dual purpose electrode assembly, accordingto the invention, the need for replacing a neuron-monitoring electrodesupport with a lesion-producing electrode support is eliminated, andconsequently the risk of error in electrode support misplacement is alsoeliminated.

Furthermore, the safety and efficacy of pallidotomy is stronglyinfluenced by the ability to effectively monitor and assess brain tissuebeing considered for inactivation. The ability to monitor a number ofneurons over an extended period of time, on the ward, allows for thegathering of more precise information on the physiologic status of eachneuron, and a more informed decision to be made on which regions of thetissue are to be targeted for lesion production.

iii. HOP Risk/Benefit

One potential or apparent drawback to use of the HOP in obesitytreatment may be the public perception of stereotactic probe placementwithin the brain as a high risk procedure. In reality, statisticsindicate that electrode implantation within the human brain is a lowrisk procedure. Therefore, the risks of mortality and morbidityassociated with morbid obesity probably greatly exceed those associatedwith electrode implantation. On this basis, the use of the HOP for thetreatment of morbid obesity can be justified as having a lowrisk/benefit ratio.

The foregoing embodiments are merely exemplary and are not to beconstrued as limiting the present invention. The present teaching can bereadily applied to other types of apparatuses. The description of thepresent invention is intended to be illustrative, and not to limit thescope of the claims. Many alternatives, modifications, and variationswill be apparent to those skilled in the art.

1. A drug infusion device, comprising: a macrocatheter; and a pluralityof microinfusion catheters disposed non-coaxially side-by-side withinthe macrocatheter, wherein at least one microinfusion catheter comprisesa plurality of drug delivery ports and is configured to receive a drugand infuse the drug into a tissue of a patient, and wherein theplurality of drug delivery ports comprises individually controllabledrug delivery ports.
 2. A drug infusion device, comprising: a pluralityof microinfusion catheters disposed non-coaxially side-by-side withrespect to one another and configured to receive a drug and infuse thedrug into a tissue of a patient, wherein at least one microinfusioncatheter comprises a plurality of individually controllable drugdelivery ports disposed along a length of the at least one microinfusioncatheter; and a macrocatheter configured to house the plurality ofmicroinfusion catheters.
 3. The drug infusion device of claim 2, whereinthe tissue comprises the hypothalamus.
 4. The drug infusion assembly ofclaim 2, wherein the macrocatheter comprises a magnet configured tocooperate with an external magnetic field to guide the macrocatheter. 5.A drug infusion assembly comprising the drug infusion device of claim 2,and further comprising a pump configured to deliver the drug to at leastone microinfusion catheter of the plurality of microinfusion catheters.6. The drug infusion assembly of claim 5, wherein the pump is configuredto be controlled percutaneously.
 7. The drug infusion assembly of claim5, further comprising a manifold configured to convey the drug from thepump to the at least one microinfusion catheter.
 8. A drug infusiondevice, comprising: a macrocatheter; and a plurality of microinfusioncatheters disposed non-coaxially side-by-side within the macrocatheter,wherein at least one microinfusion catheter of the plurality ofmicroinfusion catheters is movable and comprises a plurality ofindividually controllable drug delivery ports, wherein the at least onemicroinfusion catheter is configured to receive a drug and infuse thedrug into a tissue of a patient, and wherein the macrocatheter comprisesa magnet configured to aid in the stereotactic placement of themacrocatheter in the tissue.
 9. The drug infusion assembly of claim 1,wherein the magnet comprises a magnetic collar disposed on themacrocatheter proximate to an end of the macro catheter.
 10. A druginfusion device, comprising: a macrocatheter; a plurality ofmicroinfusion catheters disposed non-coaxially side-by-side within themacrocatheter, wherein at least one of said plurality of microinfusioncatheters comprises a plurality of drug delivery ports and is configuredto receive a drug and infuse the drug into a tissue of a patient; and atleast one pump configured to controllably supply the drug to the atleast one microinfusion catheter, wherein the at least one pump isconfigured to be controlled percutaneously.
 11. The drug infusionassembly of claim 10, further comprising a manifold configured to conveythe drug from the at least one pump to the at least one microinfusioncatheter.
 12. A drug infusion device, comprising: a plurality ofmicroinfusion catheters disposed non-coaxially side-by-side with respectto one another and configured to receive a drug and infuse the drug intothe hypothalamus of a patient; a pump configured to controllably supplya drug to the plurality of microinfusion catheters; and a manifoldconfigured to convey the drug from the pump to the plurality ofmicroinfusion catheters, wherein at least one microinfusion cathetercomprises multiple individually controllable drug delivery portsdisposed along a length of the at least one microinfusion catheter. 13.A drug infusion device, comprising: a plurality of microinfusioncatheters disposed non-coaxially side-by-side with respect to oneanother and configured to receive a drug and infuse the drug into ahypothalamus of a patient; at least one electrode configured to senseelectrical activity of the hypothalamus; a pump configured tocontrollably supply a drug to the plurality of microinfusion catheters,wherein the pump is configured to communicate with the at least oneelectrode and supply the drug to at least one of the plurality ofmicroinfusion catheters in accordance with the electrical activity ofthe hypothalamus; and a manifold configured to convey the drug from thepump to the plurality of microinfusion catheters.
 14. A drug infusionassembly for microinfusing a drug into the hypothalamus of a patient'sbrain, comprising: a plurality of microinfusion catheters disposednon-coaxially side-by-side with respect to one another and configured tobe inserted into the hypothalamus of a patient's brain, wherein at leastone microinfusion catheter of said plurality of microinfusion catheterscomprises a plurality of drug delivery ports arranged such that eachdrug delivery port of the plurality of drug delivery ports is configuredto deliver a drug to a separate site within the hypothalamus; amacrocatheter for housing the plurality of microinfusion catheters; adrug delivery manifold, wherein each of said plurality of microinfusioncatheters is functionally coupled to said drug delivery manifold; a drugsupply line functionally coupled to said drug delivery manifold; and adrug reservoir and pump for retaining and for pumping a drug, said drugreservoir and pump being functionally coupled to said drug supply line,wherein said drug reservoir and pump are capable of pumping a drug at avariable rate, and the variable rate can be controlled percutaneously.15. The drug infusion assembly as claimed in claim 14, wherein saidmacrocatheter includes a magnetic unit, said magnetic unit beingconfigured such that application of an external magnetic field allowsfor stereotactic placement of said macrocatheter to a specific locationwithin the patient's brain.
 16. The drug infusion assembly as claimed inclaim 14, wherein said macrocatheter includes a magnet located at adistal end of said macrocatheter.
 17. The drug infusion assembly asclaimed in claim 14, wherein said drug reservoir and pump are capable ofpumping a drug at a variable rate.
 18. The drug infusion assembly asclaimed in claim 14, wherein said drug reservoir and pump include arecharge valve for recharging said drug reservoir and pump with a drug.19. The drug infusion assembly as claimed in claim 18, wherein saidrecharge valve is accessible percutaneously.
 20. The drug infusionassembly as claimed in claim 14, wherein the drug reservoir and pumpcontains and supplies an appetite controlling drug for treating obesity.21. The drug infusion assembly as claimed in claim 14, wherein at leastone microinfusion catheter of the plurality of microinfusion cathetersis configured such that each of the plurality of drug delivery ports canbe independently controlled.
 22. The drug infusion assembly as claimedin claim 14, further comprising monitoring electrodes which senseelectrical activity within the patient's hypothalamus.
 23. The druginfusion assembly as claimed in claim 22, wherein the at least onemicroinfusion catheter of the plurality of microinfusion catheters isconfigured to independently deliver a drug from each of the plurality ofdrug delivery ports of the at least one microinfusion catheter based oninformation gathered from the monitoring electrodes.
 24. The druginfusion assembly of claim 14, wherein the plurality of drug deliveryports is disposed along a length of the at least one microinfusioncatheter.
 25. The drug infusion assembly as claimed in claim 14, whereinsaid drug reservoir and said pump comprise a combined drug reservoir andpump.
 26. A drug infusion device, comprising: a macrocatheter; aplurality of microinfusion catheters extending through the macrocatheterand movably disposed non-coaxially side-by-side with respect to oneanother, wherein each of the plurality of microfusion catheters isconfigured to receive a drug, and wherein an end portion of each of theplurality of microinfusion catheters is configured to extend beyond anend of the macrocatheter so as to infuse the drug into the hypothalamusof a patient; a pump configured to controllably supply a drug to theplurality of microinfusion catheters; a manifold configured to conveythe drug from the pump to the plurality of microinfusion catheter; andat least one electrode configured to sense electrical activity of thehypothalamus, wherein the pump is configured to communicate with the atleast one electrode and supply the drug to at least one of the pluralityof microinfusion catheters in accordance with the electrical activity ofthe hypothalamus.
 27. The drug infusion assembly of claim 26, whereinthe pump can be controlled percutaneously.
 28. The drug infusionassembly of claim 26, wherein at least one microinfusion cathetercomprises multiple individually controllable drug delivery portsdisposed along a length of the at least one microinfusion catheter. 29.The drug infusion assembly of claim 26, wherein the macrocathetercomprises a magnet.
 30. The drug infusion assembly of claim 26, whereinthe drug is configured to affect the weight of the patient.
 31. A druginfusion device, comprising: a macrocatheter, comprising a magnetconfigured to aid in the stereotactic placement of the macrocatheter,wherein the magnet comprises a magnetic collar disposed on themacrocatheter proximate to an end of the macrocatheter; and a pluralityof microinfusion catheters disposed non-coaxially side-by-side withinthe macrocatheter, wherein at least one of said plurality ofmicroinfusion catheters comprises a plurality of drug delivery ports andis configured to receive a drug and infuse the drug into a tissue of apatient, and wherein at least one of said plurality of microinfusioncatheters is movable within said macrocatheter.
 32. The drug infusiondevice of claim 31, wherein the plurality of drug delivery portscomprises individually controllable drug delivery ports.
 33. The druginfusion device of claim 31, wherein the plurality of drug deliveryports are disposed along a length of the at least one microinfusioncatheter.
 34. A drug infusion assembly comprising the drug infusiondevice of claim 31, and further comprising at least one pump configuredto controllably supply the drug to the at least one microinfusioncatheter.
 35. The drug infusion assembly of claim 34, wherein the atleast one pump is configured to be controlled percutaneously.
 36. Thedrug infusion assembly of claim 34, further comprising a manifoldconfigured to convey the drug from the at least one pump to the at leastone microinfusion catheter.
 37. A drug infusion assembly formicroinfusing a drug into the hypothalamus of a patient's brain,comprising: a plurality of microinfusion catheters disposednon-coaxially side-by-side with respect to one another and configured tobe inserted into the hypothalamus of a patient's brain, wherein at leastone microinfusion catheter of said plurality of microinfusion catheterscomprises a plurality of drug delivery ports arranged to deliver a drugto a separate site within the hypothalamus; a drug delivery manifold,wherein each of said plurality of microinfusion catheters isfunctionally coupled to said drug delivery manifold; a drug supply linefunctionally coupled to said drug delivery manifold; and a drugreservoir and pump for retaining and pumping a drug, said drug reservoirand pump being functionally coupled to said drug supply line, whereinsaid drug reservoir and pump includes a recharge valve for rechargingsaid drug reservoir and pump with a drug.
 38. The drug infusion assemblyas claimed in claim 37, wherein said recharge valve is accessiblepercutaneously.
 39. The drug infusion assembly as claimed in claim 37,wherein said drug reservoir and said pump comprise a combined drugreservoir and pump.
 40. A drug infusion assembly for microinfusing adrug into the hypothalamus of a patient's brain, comprising: a pluralityof microinfusion catheters disposed non-coaxially side-by-side withrespect to one another and configured to be inserted into thehypothalamus of a patient's brain, wherein at least one microinfusioncatheter of said plurality of microinfusion catheters comprises aplurality of drug delivery ports arranged to deliver a drug to aseparate site within the hypothalamus; a drug delivery manifold, whereineach of said plurality of microinfusion catheters is functionallycoupled to said drug delivery manifold; a drug supply line functionallycoupled to said drug delivery manifold; and a drug reservoir and pumpfor retaining and pumping a drug, said drug reservoir and pump beingfunctionally coupled to said drug supply line, wherein at least onemicroinfusion catheter of the plurality of microinfusion catheters isconfigured such that each of the plurality of drug delivery ports can beindependently controlled.
 41. The drug infusion assembly as claimed inclaim 40, wherein said drug reservoir and said pump comprise a combineddrug reservoir and pump.
 42. A drug infusion assembly for microinfusinga drug into the hypothalamus of a patient's brain, comprising: aplurality of microinfusion catheters disposed non-coaxially side-by-sidewith respect to one another and configured to be inserted into thehypothalamus of a patient's brain, wherein at least one microinfusioncatheter of said plurality of microinfusion catheters comprises aplurality of drug delivery ports arranged to deliver a drug to aseparate site within the hypothalamus; a drug delivery manifold, whereineach of said plurality of microinfusion catheters is functionallycoupled to said drug delivery manifold; monitoring electrodes that senseelectrical activity within the patient's hypothalamus; a drug supplyline functionally coupled to said drug delivery manifold; and a drugreservoir and pump for retaining and pumping a drug, said drug reservoirand pump being functionally coupled to said drug supply line, whereinthe at least one microinfusion catheter is configured to independentlydeliver a drug from each of the plurality of drug delivery ports basedon information gathered from the monitoring electrodes.
 43. The druginfusion assembly as claimed in claim 42, wherein said drug reservoirand said pump comprise a combined drug reservoir and pump.